Comprehensive Genomic, Mutation, Phylogenetic, and Statistical Analysis of the Monkeypox Virus Across Multiple Countries.

Comprehensive Genomic, Mutation, Phylogenetic, and Statistical Analysis of the Monkeypox Virus Across Multiple Countries - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Search Log in Primary site navigation Search Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Indian J Microbiol . 2025 Jan 16;65(2):1321–1344. doi: 10.1007/s12088-025-01447-2 Comprehensive Genomic, Mutation, Phylogenetic, and Statistical Analysis of the Monkeypox Virus Across Multiple Countries Imran Zafar 1, ✉ , Faheem kanwal 2 , Muhammad Azmat 2 , Ahsanullah Unar 3 , Ijaz Ali 4 , Waqas Yousaf 5 , Qurat ul Ain 6 , Mohd Ashraf Rather 7 , Nemat Ali 8 , Mohammad Rashid Khan 8 , Amandeep Singh Dhanju 9 , Rohit Sharma 10, ✉ Author information Article notes Copyright and License information 1 Department of Biochemistry and Biotechnology, Faculty of Science, The University of Faisalabad (TUF), Faisalabad, Pakistan 2 Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore, Lahore, Pakistan 3 Department of Precision Medicine, University of Campania ‘L. Vanvitelli’, Naples, Italy 4 Centre for Applied Mathematics and Bioinformatics (CAMB), Gulf University for Science and Technology, Hawally, Kuwait 5 Department of Botany, Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Punjab Pakistan 6 Department of Chemistry, Government College Women University, Faisalabad, Pakistan 7 Division of Fish Genetics and Biotechnology, Faculty of Fisheries, Rangil-Gandarbal (SKAUST-K), Ganderbal, India 8 Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia 9 Department of Agriculture, Khalsa College Ghardiwala, Hoshiarpur, 144207 India 10 Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005 India ✉ Corresponding author. Received 2023 Jun 27; Accepted 2025 Jan 7; Issue date 2025 Jun. © Association of Microbiologists of India 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. PMC Copyright notice PMCID: PMC12246335  PMID: 40655364 Abstract Our study offers a comprehensive Monkeypox virus (MPXV) analysis, utilizing innovative protocols to uncover potential vulnerabilities. We examine MPXV’s epidemiology, link to smallpox, genomics, mutation landscape, clinical features, diagnostics, therapeutics, FDA-approved drugs, clinical trials, and preventive strategies. We used various analytical methods to analyse genome data from the NCBI database (2019–2023) to assess sequence alignment, protein identification, and genome diversity. The phylogenomic analysis identified unique lineages and a mutation associated with human transmission, revealing that 24 MPXV proteins are particularly mutation-prone. Domain analysis confirmed conserved Ortho-poxvirus genes and critical regions, providing insights into MPXV’s structure, diversity, and host interaction. Additionally, we integrated clinical data, geospatial mapping, statistical analysis, and AI/ML for predictive insights on MPXV progression. We also explored bioinformatics tools and plant-based treatments, conducting in-silico studies to identify potential drug targets. Our research integrates epidemiological and genomic data to inform real-time preventive measures and optimize public health responses to MPXV. Keywords: Monkeypox virus, MPXV , Genome wide identification, Mutation analysis, Phylogeny Introduction The Monkeypox virus ( MPXV ), Poxviridae family, Chordopoxvirinae subfamily, Orthopoxvirus genus [ 1 , 2 ], is endemic in Central and West Africa and is a causative agent of an illness resembling smallpox [ 3 ]. While the vaccinia virus used in smallpox vaccinations gives communities limited protection against MPXV [ 4 ], the suspension of general vaccinations after smallpox has been eradicated has left everyone vulnerable, leading to small outbreaks [ 5 ]. It was discovered in monkeys in 1958 and identified in humans in 1970 in the Democratic Republic of the Congo (DRC). It was predominant in DRC and has spread to other African countries [ 1 , 6 ]. The family Poxviridae is a double-stranded DNA virus [ 7 ] with a more comprehensive structure than the Orthopoxvirus genus, including smallpox, MPXV , cowpox, and vaccinia viruses [ 8 ]. The control of smallpox resulted in overall less adequate protection against other orthopoxviruses and fear of raised pathogenicity or transmissibility [ 9 ]. There is ongoing controversy and variation in DNA comparison regarding the evolutionary link between smallpox and MPXV [ 10 ]. There are gaps in our knowledge about MPXV , including its entry into the host cell, replication, immune evasion, anti-apoptotic activity, modulation of ion channels, roles of histone and chromatin, and influence on the biology of the host cell, which represent a pressing need for detailed examination of the virus and the hunt for appropriate treatments and preventive measures [ 11 ]. Research gaps persist, requiring deeper insights into its molecular mechanisms, including cell entry and replication [ 12 ]. The virus's evasion of the host immune response, interference with apoptosis, and modulation of ion channels remain poorly understood[ 13 ]. The virus's epidemiology underscores the need for adaptable responses[ 14 ]. Since May 13, 2022, MPXV cases have surfaced in 12 non-endemic countries [ 15 ], primarily among men who have sex with men and are identified in clinics for primary care and sexual health [ 16 ]. Transmission modes are under investigation, with close contact and exposure to contaminated fluids and materials suspected [ 17 ]. MPXV 's incubation period spans 5–21 days [ 18 ], and though its natural history remains incomplete [ 19 ], consuming undercooked animal products might be a risk factor. Severity varies, with immune-compromised individuals more susceptible. Unlike smallpox, the West African MPXV clade is less severe but poses a threat due to waning immunity from discontinued smallpox vaccinations [ 20 ]. New vaccines, diagnostics, and antiviral agents are being developed for preparedness. The virus's intersections with smallpox, cowpox [ 21 ]., COVID-19 [ 22 ] and SARS-CoV-2 [ 23 ] variants can lead to misdiagnoses and complexities in immunity cross-reactivity [ 23 ]. WHO anticipates more cases as surveillance broadens in non-endemic countries, emphasizing education, and immediate actions to halt transmission and protect healthcare workers [ 24 ]. Therefore, in this genomic investigation, we propose to carry out mutation analysis of MPXV from various countries, as well as phylogenetic analysis and statistical analysis. The findings outline the genetic characterization of important mutations, the transmission dynamics, and the chickens' potential to act as hosts for cross-species transmission. The knowledge of MPXV’s gene pool and mutation process will help in world preparedness, introducing new vaccines and therapeutics, and better outbreak management [ 1 , 5 , 6 ]. The present study has important implications for revealing trends in the virus, enhancing the outbreak management systems, and contributing to the advancements in diagnostics and treatments adapted to the virus’s changes. This study aims to undertake a geographical distribution of the MPXV genetic variations to reach policymakers and improve cross-border preparedness and knowledge on MPXV and the risk of zoonotic spillover [ 7 , 8 ]. The significance lies in its contributions to epidemiological understanding, informing public health responses, aiding vaccine and treatment development, assessing zoonotic risks, enhancing global preparedness against outbreaks, and offering insights into the virus's evolutionary history. Material and Methods In this study, we embark on a comprehensive exploration of the MPXV , employing various analytical methodologies to comprehensively investigate multiple aspects of the MPXV, incorporating both data collection and advanced genomic analysis as shown in Fig. 1 . Fig. 1. Open in a new tab Details of applied materials and methods to investigate various aspects of the MPXV virus, incorporating both data collection and advanced genomic analysis Data Sources and Search Strategies To comprehensively understand the MPXV virus, an exhaustive systematic analysis was conducted using prominent research databases, including Science Direct, SciFinder, Google Scholar, MEDLINE, EMBASE, and Scopus. This approach ensured the incorporation of the latest scientific findings available until February 2023. Specific keywords such as “ MPXV ,” “transmission,” “mode of spread,” “fatality,” “incidence rate,” “prevention,” “diagnosis,” “vaccine,” “genomics,” “molecular mechanism,” “treatment,” “clinical trial,” “case study,” and “mechanism of action” were employed to extract relevant studies. Genomic Data Collection and Analysis To initiate the genomic investigation, comprehensive FASTA files of various MPXV virus variants were obtained from reputable sources, namely the NCBI and virological.org databases [ 25 ]. These datasets were pivotal as they represented the initial pool from which subsequent virus strains emerged [ 26 ]. The reference genome's genetic makeup and annotation were sourced from established repositories, GenBank ( Genetic Sequence Database ) and GISAID ( Global Initiative on Sharing All Influenza Data ) [ 27 ]. Sequence and Structural Analysis This study uses BLASTP ( Basic Local Alignment Search Tool for Proteins ) to identify protein identities and similarities across multiple amino acid sequences, focusing on top bit-scores to ensure accurate matches. Sequence identity is calculated by aligning protein pairs and determining the average percentage similarity. For genomic alignment, Parsnp is employed with parameters optimized for high-resolution alignment, revealing genetic relationships across DNA sequences. Additionally, MUSCLE ( Multiple Sequence Comparison by Log-Expectation ) is used to align protein sequences, identifying conserved regions and sequence variations. Default parameters in MUSCLE are adjusted as necessary to enhance alignment accuracy, capturing critical sequence homologies and structural patterns. Comparative Genomic Analysis We conduct a comparative genomic analysis to evaluate the genetic similarities and differences among MPXV strains from various countries. This approach enables us to identify conserved regions within the virus's genome, which is crucial for developing diagnostic tools, therapeutics, and vaccines [ 28 ]. Additionally, comparative genomics allows us to track the emergence of new variants, assessing their potential implications for global health. By comparing genetic sequences across different regions, we gain valuable insights into the virus's evolution and its potential to adapt, ultimately informing strategies for controlling its spread and mitigating health risks [ 29 ]. Evolutionary and Phylogenetic Analysis MPVX is used as a reference for mutation screening to identify journal-based searches and detect genetic variants and mutations. In this study, we perform a comparative analysis of several stains from various countries using textual approaches as per the method of earlier researchers [ 30 – 32 ]. We used PROVEAN ( Protein Variation Effect Analyzer ) and MutPred ( Mutation Prediction ) to evaluate the possible effects of mutations on protein structure and function. Additionally, SIFT ( Sorting Intolerant From Tolerant ) and PolyPhen ( Polymorphism Phenotyping ) methodologies were used to predict the functional impact of amino acid alterations. To assess genetic variability, we use ClinVar and the single nucleotide polymorphism ( dbSNP ) database for comparative analysis and annotation of recognized genetic variations. Additionally, ANNOVAR and VEP ( Variant Effect Predictor ) are used to predict the specific annotation of genetic alterations by integrating data from various sources. Protein Motifs and Domain Analysis Various bioinformatics techniques are used to predict protein motifs and perform domain analysis. Preliminary sequence comparisons are performed using BLAST ( Basic et al . ) and HMMER ( Hidden Markov Model for Sequence Alignment ) to identify commonalities with previously found motifs and domains. The protein sequences were classified into distinct families, and conserved domains were identified using the Hidden Markov Models ( HMM ) profile and domain prediction techniques supported by InterProScan and Pfam. Multiple sequence alignment is used to identify conserved regions, while Dali's structure-based techniques identify structurally similar motifs. The functional annotations provided by Gene Ontology contribute to the analysis by elucidating the biological functions associated with the identified motifs and domains. The essential regions of proteins are predicted using MEME ( Multiple Em for Motif Elicitation ). In contrast, the NCBI-ORF ( National Center for Biotechnology Information-Open Reading Frame ) finder is used to identify DNA regions that can potentially be used in protein synthesis. The open reading frames ( ORFs ) refer to the specific areas within proteins that are synthesised and provide a clear understanding of the roles of genes and their connections within families. The open reading frames (ORFs) in DNA and the expected conserved regions in proteins are analysed. We also applied machine learning techniques to predict the accuracy of the analysis. The efficient interpretation and transfer of results through the visualisation of MEME ultimately facilitate a thorough understanding of protein structure, function, and evolutionary relationships. Mutation Screening We use MPVX as a reference for mutation screening to identify review-based searches and genetic variants and mutations. Using texting methodologies, we compare it with various stains obtained in different countries. To assess the potential impacts of mutations on protein structure and function, we used software tools such as PROVEAN ( Protein Variation Effect Analyzer ) and MutPred ( Mutation Prediction ). The functional effect of amino acid modifications was predicted using SIFT ( Sorting Intolerant From Tolerant ) and PolyPhen ( Polymorphism Phenotyping ) techniques. To conduct comparative analysis and annotation of established genetic variations, we use ClinVar and the single nucleotide polymorphism ( dbSN P) database to assess genetic variability. Additionally, we use ANNOVAR and VEP ( Variant et al. ) to predict the particular annotation of genetic changes by combining data from different sources. Clinical Investigation The clinical examination of MPXV includes several elements, including surveillance, epidemiological analysis, laboratory diagnosis, treatment options, vaccination programs, and dissemination techniques. We identify suspected cases from review-based literature, confirmed by laboratory analyses, such as PCR and serological tests based on meta-analysis. We also use text mining techniques and bioinformatics approaches to analyze data and keep information safe with blockchain [ 33 – 36 ]. We collect data based on available treatment methods implemented per recognised criteria, including administering antiviral drugs and providing supportive care, and make consequences for future implementations. The effectiveness of these therapies is evaluated by evaluating the therapy outcomes from meta-analysis and listing the results related to these types of trials, providing a clearer picture of disease involvement. Geospatial Mapping In this study, we employ geospatial mapping techniques to visually represent the geographical distribution and genetic diversity of the virus. By integrating genomic data with geographic coordinates, we plot viral variants across maps to identify regional hotspots of genetic variation and track potential transmission routes. This method allows us to analyze how the virus has spread over time, highlighting areas with high concentrations of specific mutations and revealing patterns of transmission, including cross-border movement. The use of temporal mapping further enhances our understanding of the virus's evolutionary dynamics, helping to predict future spread and inform targeted public health strategies. Through this approach, we aim to provide a comprehensive analysis of the virus's geographic and genetic patterns, supporting more effective containment and intervention efforts. Validation and Reporting To obtain accurate and reliable identification of genetic variation, we use GATK ( Genome Analysis Toolkit )-related modified parameters. Cross-validation with public databases such as NCBI (National Center for Biotechnology Information), BLAST ( Basic Local Alignment Search Tool ), or EMBOSS ( European Molecular Biology Open Software Suite ) was used to align sequences and validate the status of mutations. Simulations using known mutations were performed with SimuPOP ( Simulation of Population Genetics software ) or MSPRIME MSPRIME ( Multiple Sequence Pairwise Rearrangement Inference Method). Analytical tools, including Biopython ( A set of tools for computational biology in Python ) and R Bioconductor ( An open-source software project for the analysis of genomic data using R programming language ), were applied for random sampling and resampling. Genomic prediction was made based on online available data in different bioinformatics-indigitated databases. BLAST and MEGA ( Molecular Evolutionary Genetics Analysis ) were applied for sequence alignment and analysis in comparative genomics. Structural analysis programs were used to visualize and predict protein structures and validate their essential information. Network analysis was predicted, and interaction was visualized in mutation sites. The compact details of statistical values were investigated to confirm the accuracy and reproducibility of genomic results without additional experimental methods. Statistical Analysis Descriptive and inferential analysis methods were used as per data collected. The normality of the data was tested using Shapiro Wilk’s test while the transformation of the data was done where necessary. For the parametric data, analysis of variance ( ANOVA ) was used for normally distributed data and the Kruskal–Wallis test for non-parametric data; post-hoc Tukey tests for between-group comparisons of significant variables were also used. The distribution of mutation types and their potential effects on protein structures were compared using chi-square tests. To explore the correlation between mutation frequencies and geographical distribution, Pearson’s correlation coefficient was used and, for the analysis of the odds of mutation occurrence across different MPXV strains while controlling for potential confounding factors, logistic regression was applied. Data were analysed using significance level of p < 0.05, and 95% confidence intervals for all estimates were obtained. For genomic prediction models, a cross-validation with k = 10 was used in order to evaluate the models and to prevent overfitting. The degree of genomic variation was measured by Shannon and Simpson’s diversity indices and the validity of the genomic variation-Disease Outcomes hypothesis was evaluated by the use of univariate Kaplan–Meier curves and Cox proportional hazard models. All the analyses were done using the ‘R Bioconductor’ with packages such as; ‘ggplot2’, ‘dplyr’ and ‘survival’ in terms of data processing. The data were based on mean ± standard deviation for quantitative data and percentage for qualitative data where the level of significance was set at 0.05. Results and Discussions In our results, we gain a profound understanding of MPXV and systematically divide our analysis journey into distinct phases. Beginning with In-silico analysis, we unravel the virus's genetic code, paving the way for high-throughput technologies to screen for interventions rapidly. Molecular Analysis and Identification delve into the virus's molecular intricacies while analyzing symptoms and transmission dynamics to guide our epidemiological comprehension. We harness Digital Health Solutions to monitor and disseminate vital information. Pharmacological Analysis and Clinical Trials we reported to check the details of advanced therapeutic development. Ethnobotany studies merge Indigenous knowledge with ecology, and, finally, MPXV prevention and control strategies draw from all phases to form a comprehensive defense against this viral threat, ensuring multiple holistic approaches. Molecular Analysis and Identification The molecular analysis and identification results of MPXV are derived from comprehensive reviews, publications, and meta-analytic studies of pre-existing research. To validate the established sampling procedures, where researchers extract nucleic acid from multiple viral genetic material isolates, control methods are used and confirm the accuracy of previous sampling methods as per the method Nunes et al. [ 37 ]. The investigator used real-time PCR (qPCR) and Polymerase Chain Reaction (PCR) techniques to amplify and determine specific genomic regions of MPXV throughout the evaluation process. The revised and performed sequencing technologies provide comprehensive genetic sequences that allow comparison of existing literature and meta-analysis data. Bioinformatics tools were employed for sequence analysis, validating results with earlier meta-analytic data [ 38 ]. Molecular Characterization Through integrating new findings, extensive literature reviews, and careful investigations, we completed a molecular characterization of the MPXV. We investigated the intricate genetic makeup of the virus using sequencing, qPCR, and PCR. Our analysis verified existing genetic markers and variations and uncovered new insights into the MPXV genome, consistent with recent studies [ 38 ], Sougrat et al. [ 39 ]. These findings support regional genetic variation and subtype diversity, as highlighted by Forni et al. [ 40 , 41 ]. The viral morphology, including the brick-shaped envelope and DNA-containing nucleocapsid, also matched previous descriptions [ 42 ]. These findings support regional genetic variation and subtype diversity, as highlighted by Quarleri et al. [ 41 , 43 ]. The details of MPXV Size, ORFs, and Genetic Variations Across Different Strains are mentioned in Table 1 . Table 1. Comparing Genomes: Size, ORFs, and Genetic Variations Across Different Strains Strain Genome Size (kb) ORFs Structural Differences Reference West African MPXV ~ 220 245 Larger genome size than Congo Basin MPXV , with an additional 44 ORFs [ 39 ] Contains a 10-kb deletion in the CrmB gene region that may affect virulence Congo Basin MPXV ~ 200 204 Smaller genome size than West African MPXV [ 37 ] Contains a 27-bp deletion in the A-type inclusion protein gene that may affect the host range MPXV ZAI-79 ~ 210 210 Contains a deletion in the C11L gene, which is associated with host range restriction [ 38 ] It contains a unique 7-kb genomic segment MPXV ZAI-96 ~ 210 213 Contains an additional ORF, Z6R, which is absent in other MPXV strains [ 44 ] It contains a unique 7.5-kb genomic segment MPXV USA-2003 ~ 215 209 Contains an amino acid substitution in the A56R protein that is associated with reduced virulence in humans [ 39 ] Contains a 16.6-kb genomic deletion in the right terminal region Open in a new tab Anti-Apoptotic Mechanism of the MPXV Virus The present work highlights multiple anti-apoptotic strategies MPXV uses to promote host cell viability and viral reproduction. We found similar results to Reynolds [ 45 ], who noted the importance of viral proteins such as CrmB and SPI-2 in inhibiting apoptotic cell death mediated through TNF signaling and caspase activation. Similarly, Pinto [ 46 ] realized that MPXV alters the expression of apoptosis-related genes such as NOXA and caspase three while reducing the Bcl-2 anti-apoptotic genes. Furthermore, it is based on et al. [ 46 ], who described the mechanism of action of viral proteins of Bcl-2 and Bcl-xL in stabilising the mitochondrial membrane and preventing cytochrome c release and inhibition of the intrinsic apoptotic pathway. This agrees with our work on how MPXV creates biofilms to subvert apoptosis of host cell mitochondria. In additionally to the findings mentioned above, our work expands the study of Bowie [ 47 ], who described the effect of MPXV on a cell’s ability to regulate the actin cytoskeleton, by uncovering more of the ways the virus influences cellular functions such as membrane voltage and small GTPases including, ROCK1 and SOS2. Our study is also in line with [ 48 ], who noted that M11L suppresses apoptosis by binding to the mitochondria-located pore complex, which agrees that MPXV employs complex strategies to promote host cell survival. Altogether, the data presented here support and expand the previous work and, therefore, are helpful for a better understanding of viral interactions with host cellular systems, which is critical for designing efficient antiviral treatments. MPXV Symptoms to the Transmission Analysis This section embarks on a comprehensive exploration of MPXV , ranging from an in-depth examination of its symptoms to a detailed analysis of its modes of transmission. Delving into the clinical manifestations, epidemiological aspects, and transmission dynamics, we seek to unravel the multifaceted aspects of this viral disease. MPXV : A Public Health Crisis The dissemination of MPXV differs from other widespread diseases such as Flu and COVID-19 [ 49 ]. It primarily spreads through close and intimate contact, including sexual contact. Currently, it mainly affects men who engage in sexual activities with other men, but it can also spread among close family members with less efficiency. Despite this, it is not a highly contagious ailment, far from the transmissibility of COVID-19 or Flu. Usually, contact must last for more than three hours within a distance of six feet, and direct contact with the skin lesions is necessary. The transmission can also occur through contaminated textiles and clothing. The World Health Organization has not deemed a global public health crisis, as it has not yet spread extensively in communities. However, if the pattern of transmission changes, including droplet transmission, the WHO may reevaluate it as a crisis. Biological Pathways of the MPXV Virus Zoonotic transmission from animals to humans can take place by direct contact with the blood, bodily fluids, and lesions of infected creatures, found in animals such as rope squirrels, tree squirrels, Gambian pouched rats, dormice, monkeys, and others in Africa [ 50 , 51 ]. The natural host of the MPXV is yet to be identified, but rodents are the most likely candidates[ 52 ]. The consumption of undercooked animal products from infected animals is a potential risk factor. People residing near forested regions may have occasional exposure to infected animals. Human-to-human transmission can happen through contact with respiratory secretions, skin lesions, or recently contaminated objects. Droplet respiratory transmission usually demands long-term face-to-face contact, making household members, health workers, and close contacts of active cases more vulnerable. However, the longest documented chain of transmission within a community has risen to 9 successive person-to-person infections in recent years, potentially due to declining immunity from the cessation of smallpox vaccination. The transmission can also happen during pregnancy from mother to fetus (resulting in congenital MPXV ) or during close contact during and after birth. Although close physical contact is known to be a significant risk factor, the possibility of transmission through sexual routes is yet to be established through proper studies. MPXV spreads through contact with skin lesions, fluids, or scabs, though not yet confirmed via semen or vaginal fluids. Transmission can also occur through contaminated items, respiratory droplets, or to a fetus in pregnant individuals. Infected individuals are contagious from symptom onset until scabs form, which can take up to 4 weeks [ 53 , 54 ]. Isolation is recommended. To prevent spread, avoid close contact, including sexual activities and sharing potentially contaminated items. According to the CDC, testing relies on an Orthopoxvirus assay, with positive cases presumed as MPXV in the U.S. Signs and Symptoms MPXV symptoms typically appear 6 to 13 days after infection (5–21 days). The initial phase, lasting up to 5 days, includes fever, severe headache, swollen lymph nodes, and more [ 55 ]. MPXV is distinguished by lymphadenopathy. A rash follows in 1 to 3 days, often on the face and limbs. It can affect various body parts, progressing from macules to crusts. Symptoms last 2 to 4 weeks, longer in severe cases [ 56 ]. Complications include infections, pneumonia, encephalitis, and vision loss; more detail and description are mentioned in Fig. 2 . Fatality rates range from 0–11%, recently 3–6%. The virus can be transmitted to others during illness, especially those with weak immune systems. Fig. 2. Open in a new tab MPXV main Signs and symptoms Statistical Analysis of MPXV Cases Since January 1, 2022, WHO has received reports of MPXV cases from 114 Member States across all six regions, totaling 89,529 confirmed cases, 662 probable cases, and 156 deaths as of August 22, 2023, notably since May 13, 2022, cases have surged in countries with no prior MPXV transmission, marking the first sustained transmission outside West and Central Africa. Except for select countries in these regions, the outbreak mainly affects men who have sex with men without signs of widespread transmission. Even one case in a country is considered an outbreak. The emergence of MPXV in diverse regions without direct links suggests hidden transmission. Global risk is rated moderate, along with African, Eastern Mediterranean, European, and American regions; risk is low in South-East Asia and Western Pacific. On September 16, 2023, the IHR Emergency Committee declared the outbreak no longer an international concern and issued revised recommendations for a long-term control strategy. Weekly new cases globally dropped 82.8% in week 33 (Aug 14–20) to 98 cases from week 32 (Aug 7–13) at 571 cases. Most recent cases came from the Western Pacific (65.5%) and the Americas (21.8%). Top 10 affected countries: USA (30,534), Brazil (10,967), Spain (7,565), France (4,150), Colombia (4,090), Mexico (4,050), Peru (3,812), UK (3,771), Germany (3,694), and Canada (1,496), comprising 82.8% of global cases. In the latest whole reporting week, five countries saw case increases, the highest in Thailand; in the last 21 days, 18 countries reported cases; in the past 7 days, Malaysia reported the first case on September 16, as mentioned in Fig. 3 . Fig. 3. Open in a new tab Data on the 2022 MPXV outbreak is collated by the World Health Organization and is updated as new information is reported Diagnostic Criteria for MPXV MPXV can be diagnosed by clinical symptoms and laboratory testing [ 57 ]. Clinical symptoms can include fever, headache, muscle aches, and a rash progressing to bumps and scabs [ 58 ]. However, these symptoms can also be present in other infectious diseases, making laboratory confirmation necessary. Laboratory testing can involve the detection of viral DNA, antigens, or antibodies in samples such as blood, skin lesions, or respiratory secretions to diagnose MPXV. This can be done using techniques such as polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), or other serological tests. Isolation of the virus in cell culture can also be used for diagnosis. Proper sample collection and transport to a laboratory equipped for appropriate testing is crucial for a confirmed diagnosis of MPXV . Polymerase chain reaction (PCR) testing is the most accurate and sensitive method for diagnosing MPXV , with skin lesion samples from vesicles, pustules, and dry crusts being the preferred specimens. If available, biopsy may also be an option. Specimens must be stored in dry, sterile tubes and kept calm. Blood PCR tests are not recommended as they often yield inconclusive results due to the short duration of virus presence in the blood. However, it is essential to note that laboratory testing should be conducted in a biosafety level 3 (BSL-3) laboratory due to the potential risk of exposure to the virus. In addition, clinical and epidemiological factors should also be taken into account when making a diagnosis of MPXV , such as exposure to infected animals or humans. Diagnosing MPXV requires carefully examining the patient's symptoms, medical history, and laboratory testing results. Health workers must take into account other illnesses with similar symptoms, including chickenpox, measles, bacterial skin infections, scabies, syphilis, and drug-induced allergies. Distinguishing features, such as lymphadenopathy during the early stages of illness, can help differentiate MPXV from similar conditions. Immunohistochemistry is a technique used to visualise viral antigens within tissue samples, providing valuable insights into the location of the virus and the extent of infection. Next-Generation Sequencing (NGS) is a technology that offers genetic insights into the virus, improving our understanding of its epidemiology and evolutionary patterns. POCT devices provide rapid on-site testing, particularly beneficial in resource-constrained situations or during epidemics. These devices offer rapid diagnosis, enabling better patient care and public health interventions. Serological and antigen detection methods are not recommended for diagnosing MPXV as they are not specific to the virus and may result in false positives, especially in individuals vaccinated with vaccinia-based vaccines. When providing test results, it is essential to accompany the specimens with relevant patient information, such as the dates of onset of fever and rash, specimen collection date, current status of the individual, and age. Digital Health Solutions for MPXV Virus In combating the MPXV , digital health innovations have emerged as a transformative force. These technologies offer a multifaceted approach to addressing the virus's challenges, from telemedicine to mobile applications. They empower real-time disease surveillance, enable remote consultations, and provide vital information on symptom monitoring and preventive measures. Digital solutions facilitate contact tracing, data sharing for research, and the efficient distribution of vaccines and supplies. In this era of digital healthcare, harnessing technology enhances our response to MPXV and strengthens our overall preparedness and resilience in the face of emerging infectious diseases. Roles of Technologies for MPXV Diagnosis The integration of AI, DL, ML, big data, bioinformatics, blockchain, innovative health, and cloud computing can significantly improve the diagnosis of MPXV , as mentioned in Fig. 4 . These technologies can analyze medical images, symptoms, and large datasets of medical records, lab results, and demographic information to support clinicians in decision-making, identify outbreaks, and track the spread of the virus. Additionally, they can improve the accuracy and speed of diagnoses, reduce the spread of the virus, and provide insights into the epidemiology of MPXV . It is important to note that the use of these technologies for MPXV is still in its early stages and requires further research and validation before it can be widely adopted. Additionally, these technologies' accuracy depends on the quality and diversity of the data used to train them, so it is essential to ensure that the algorithms are trained on representative and diverse datasets. Various technologies play crucial roles in MPXV diagnosis: AI assists clinicians by analyzing medical images and symptoms, facilitating rapid outbreak identification through extensive dataset analysis [ 59 ]; DL identifies skin rash patterns and assesses risk factors in medical records and demographics [ 60 ]. Fig. 4. Open in a new tab Roles of various technologies for MPXV Diagnosis ML supports clinicians with image and symptom analysis and identifies outbreaks [ 61 ]; Big Data handles vast medical records, lab results, and demographics to enhance early outbreak detection and understanding of MPXV spread [ 62 ]. Bioinformatics analyses virus genetic sequences and identifies patterns and risk factors [ 63 ]; Blockchain ensures secure storage and sharing of medical data for transparent tracking, aiding outbreak identification and understanding virus dissemination; Smart Health enables remote monitoring of potentially exposed individuals and improves diagnostic accuracy, while Cloud Computing processes extensive data for early outbreak detection and supports remote monitoring and management of exposed individuals [ 64 ]. Major Roles of Bioinformatics In the case of MPXV , bioinformatics plays a crucial role in understanding the virus's genetic makeup and evolution [ 65 ]. By comparing the genetic sequences of different MPXV viruses, researchers can identify specific mutations or genetic variations that may be responsible for differences in virulence or transmission. This information can then be used to develop more effective diagnostic tests and treatments. One critical application of bioinformatics in MPXV diagnosis is the development of rapid molecular tests that can detect the virus in patient samples. These tests rely on PCR (polymerase chain reaction) technology to amplify and detect specific DNA sequences from the virus. Bioinformatics tools can help design primers and probes particular to MPXV , reducing the risk of false positives or cross-reactivity with other related viruses. In addition, bioinformatics can also aid in the development of antiviral drugs and vaccines for MPXV . By analyzing the genetic sequences of the virus, researchers can identify potential targets for drug development or vaccine design. For example, some studies have identified specific proteins critical for viral replication or host-cell interactions, which drugs or vaccines could target. In short, bioinformatics plays a significant role in MPXV research by analyzing genetic sequences, constructing evolutionary trees, identifying drug targets, developing vaccines, and integrating data from multiple sources. By leveraging the power of computational analysis and genetic sequencing, researchers can gain deeper insights into the biology of the virus, track its spread, and develop more effective strategies for diagnosis and treatment. Bioinformatics also helps identify potential biomarkers for disease diagnosis and prognosis and develop more targeted interventions and control strategies tailored to the specific needs of different populations [ 66 ]. Insilco Analysis We performed In-silico analysis to study the genetic makeup of the MPXV using advanced bioinformatics tools and analyze the primary annotation in the virus's genome for its screening about origins, mutations, and potential weaknesses. Genomic Status of MPXV Virus The complete genome sequence of the current MPXV outbreak provides valuable insights into the virus, its evolution, and its potential impact [ 67 ]. Analyzing this genetic data allows for comparisons with previous outbreaks [ 68 ]. We explore multiple strains of MPXV , as mentioned in Table 2 ; in our observations, the MPXV _USA_2022_MA001 sequence closely resembles the 2017–18 outbreak strains, differing in only a few nucleotide pairs. The resulting data aids in understanding the virus's spread and evolution for public health awareness, as detailed in earlier researchers' studies [ 67 ]. Annotation of these genomic sequences in GenBank benefits the broader scientific community and provides potentially leading discoveries as per the study by [ 67 ]. It underscores the importance of timely disease surveillance and response [ 69 ]. Table 2. Multiple Genome variants for Insilco analysis and investigation Accession ID Genomic length Accession ID Genomic length Accession ID Genomic length MN702451.1 190,413 bp MN346694.1 198,406 bp MT724770.1 191,537 bp MN702452.1 190,244 bp MN346695.1 198,361 bp MT724771.1 190,352 bp MN702453.1 189,632 bp MN346696.1 198,365 bp MT724772.1 190,615 bp MT250197.1 197,551 bp MN346697.1 198,381 bp MT903337.1 197,547 bp MN346690.1 198,441 bp MN346698.1 198,298 bp MT903338.1 197,559 bp MN346691.1 198,577 bp MN346699.1 198,298 bp MT903339.1 197,556 bp MN346692.1 198,412 bp MN346700.1 198,298 bp MT903340.1 197,209 bp MN346693.1 193,146 bp ON585030.1 197,208 bp MT903341.1 185,309 bp ON585035.1 197,220 bp ON585031.1 197,208 bp MT903342.1 197,309 bp ON585036.1 197,198 bp ON585032.1 197,211 bp MT903343.1 197,134 bp ON585036.1 197,198 bp ON585033.1 197,220 bp MT903344.1 197,233 bp ON585038.1 196,305 bp ON585034.1 197,208 bp MT903345.1 197205 bp ON595760.1 196,254 bp ON563414.2 197,124 bp MT903346.1 198,778 bp ON568298.1 197,378 bp MT724769.1 190,181 bp MT903347.1 198,780 bp MN702444.1 190,167 bp MN702446.1 190,357 bp MT903348.1 198,780 bp MN702445.1 190,519 bp MN702447.1 189,841 bp MN702447.1 189,841 bp MN702448.1 189,838 bp MN702449.1 190,270 bp MN702450.1 190,264 bp Open in a new tab The rapid identification and subsequent submission of the MPXV genome sequence to GenBank underscores the critical importance of the genome sequence in advancing global efforts to combat infectious diseases [ 70 ]. A more comprehensive understanding of the evolutionary mechanisms of the MPXV genome can be achieved through a comparative analysis, particularly about strains from previous outbreaks (Organization, 2021), where significant similarities and nuanced distinctions can be seen [ 71 ]. An in-depth examination of the structure of the genome reveals an intricate molecular blueprint characterized by a tightly arranged set of genes, where variable terminal segments influence host range and ability to cause disease [ 72 ]. In contrast, conserved core genes regulate essential cellular functions [ 73 ]. Figure 5 illustrates the genomic structure of approximately 200 kilobases in size and encodes around 200 proteins. MPXV has a linear, double-stranded DNA structure with hairpin-like closures at both ends and 10 kilobases of inverted terminal repeats (ITRs) at each terminus. The genetic sequencing of viruses is crucial for monitoring infectious diseases [ 74 ], but the MPXV outbreak poses challenges due to its slow genomic evolution compared to RNA viruses [ 75 ]. Surprisingly, recent reported outbreak sequences reveal more mutations than expected, considering poxviruses' slow evolution. These mutations raise questions about the virus's origins and spread, offering new insights for outbreak control [ 41 , 76 ] Fig. 5. Open in a new tab MPXV Virus Genome structure: A represents the MPXV virion, and B represents the MPXV genome MPXV Virus Syntenic Analysis The syntenic organization of the MPXV genome provides valuable information on the evolution of species, genome organization, and host-parasite relationship. MPXV had preserved domains with other Orthopoxviruses, such as variola and vaccinia, necessary for replication and transcription. Prior studies [ 77 , 78 ] noted that these conserved areas are involved in replicating viruses. The current examination also substantiates this hypothesis since unique sequence blocks are characteristic of genomic organization and replication mechanisms, as well as encoding structural proteins such as the significant enveloped antigen, as observed in the 2019 analysis of Guo et al. [ 78 ], and the 2021 study by Pecori et al. [ 79 ]. As with the preceding survey of Pecori et al. [ 79 ], the mutation rate of rate viruses is quite conservative, ranging from 10^-5 to 10^-6 mutations per restricted replication site. Still, it can rise due to recombination or acquisition of foreign genes, as with MPXV genetic variability. For example, in the second group, we compared other MPXV’s distinct genomic features that may define its virulence and host range as compared to other previously sequenced viruses, thus replicating the earlier findings by Pecori et al. [ 79 ] for similar unique sequences involved in viral pathogenesis. Besides, as pointed out by et al. [ 80 ], MPXVs are deposited in public repositories like GenBank (NCBI) and thus facilitate comparative genomic analysis that offers an enhanced understanding of the MPXV evolution and chances of developing therapeutics. This analysis identified several conserved genomic regions shared among various poxviruses, as shown in Fig. 6 . Given its evolutionary history with other Orthopoxviruses, these results are essential for improving our und of MPXV and its ability to mutate and adapt. Fig. 6. Open in a new tab Syntenic Analysis of MPXV Genome: Implications for Host Range and Vaccine Development Mutational Analysis The mutational changes seen in the human MPXV virus have profound implications for that virus life cycle and the pathogenic potential of the virus. The virus synthesizes several proteins essential for aspects like virus replication, entering the host cell, and even evading the host’s immune system [ 80 ]. Mutations in these genes can impact the successful performance of some related processes, the ability of the virus to escape the immune system responses, and the capacity to cause disease [ 29 , 81 ]. For example, mutations on the virus's exterior can change the proteins on its surface, enabling it to break through immune barriers. In contrast, other mutations affecting enzymes that replicate the virus can change its pathogenicity and how infectious the virus is [ 82 ]. Our study found numerous mutations common to all the MPXV strains affecting viral behavior, as shown in Table 3 . Thus, our results indicate for the first time the link between the elevated viral pathogenicity and the obtained mutations (A226V in the H3L protein and K77E in the A6L protein) that affect the replication rate and the virus’s ability to evade the host immune system. This pattern differs from what has been observed in prior research on DNA viruses, including SARS-CoV-2, which characterize the viral evolution by mutations more frequently than any other type occurring with a higher replication rate of errors. In contrast, MPXV , as a DNA virus, usually presents a lower mutational rate than RNA viruses, such as Ebola. Our study indicates that MPXV mutations may occur in response to host immunity and not solely because of replication errors. In particular, cellular enzymes such as APOBEC3 have been carried out with the hope that they cause mutations in the mutagenesis due to an immune system attack [ 83 ]. Table 3. Detailed analysis of MPXV mutations, showcasing each mutation's location, affected protein, function, and potential impact on viral behaviour and host interactions Mutation Location Protein Function Effect A226V G2026A H3L Host cell attachment Increased virulence K77E A898G A6L Viral replication Increased replication and virulence A68T G769A A35R Host immune evasion Increased virulence and evade host immune system V123I G1378A E2L Host cell entry Increased virulence and ability to infect humans H142Y C1642T E2L Viral replication Increased replication and virulence T82I G955T A56R Host immune evasion Increased virulence and evade host immune system V207I G2364A A26L Host cell entry Increased virulence D111G C1256G E3L Immune evasion Increased virulence R277G C3155G A33R Host cell entry Increased virulence P97S C1135T A56R Host immune evasion Increased virulence V51I G590T F1L Unknown Unknown Y82C T956G A56R Host immune evasion Increased virulence D50G C561G F1L Unknown Unknown R67C C778T F1L Unknown Unknown A171V G1996T H3L Host cell attachment Increased virulence E64K G746A A35R Host immune evasion Increased virulence I103T A1217C A56R Host immune evasion Increased virulence N143S A1679G E2L Viral replication Increased replication and increased virulence S158F C1849T E2L Viral replication Increased replication and increased virulence D202Y G2332A A26L Host cell entry Increased virulence E218K A2525G A26L Host cell entry Increased virulence V229I G2669A A26L Host cell entry Increased virulence L242P T2814C A33R Host cell entry Increased virulence V260A G3015C A33R Host cell entry Increased virulence Y270H T3138C A33R Host cell entry Increased virulence Open in a new tab The current literature further supports our observation. For instance, Bécares et al. [ 84 ] detected similar mutations in MPXV strains involving H3L and A6L proteins which are associated with immune evasion and enhanced pathogenicity. According to the two, they postulated that alterations of the viral surface glycoproteins facilitated the dexterity of the virus in evading the human immune system after detection. In addition, Jiang et al. [ 85 ] revealed that mutations on the viral replication enzyme of the MPXV strains improved the viral capability in infecting human species [ 86 ]. These findings accord with our results indicating that mutations critically regulate the virus’s propensity to avoid immune recognition and enhance its pathogenicity. Moreover, another study that Taylor et al. conducted last year revealed some mutations in MPXV proteins, especially in those proteins that conceal the host immune system, and these mutations have a strong positive relation with the viral replication indices in the human cell lines [ 87 ]. These outcomes also support our result that mutations enhancing the replication of the virus and ways to evade the immune system enhance virulence. In addition, González-Paz et al. [ 88 ] mentioned that MPXV is highly adjustable in viral pathogens of human disease, confirming discrete changes in its behavior depending on host immune pressures, as indicated in the present study. Curiously, mutations associated with the current MPXV outbreak, including those in the E2L protein (V123I, N143S), are associated with viral replication in host cells [ 84 ]. It was found that these mutations may lead to the improved viral ability to infect humans, making it a worrisome sign since it may lead to the increased ability of the virus to spread with even more extensive epidemic measures. Shahriar [ 89 ] also presented this problem in their study, discussing several internal mutations of the E2L protein that increase viral replication rates and severity Bécares et al. [ 84 ]. These recent findings indicate that the changes that have taken place in MPXV’s genome are perhaps not chance occurrences but adaptations owing to immune system influence. It is a combination of multiple effects indicating that the high number of mutations observed in the current MPXV outbreak can result from the host’s immune system, for example, the APOBEC3-induced mutation process [ 83 ]. This is still known as immune editing, which generates viral strains immune to immune recognition. In Yu et al. [ 86 ] study, the authors highlight that immune editing is crucial to the virus evolution in MPXV because the incorporation range is typically lower than RNA viruses like the flu or COVID. Knowledge of these mutations is critical for the design of beneficial therapies and vaccinations. More research should be carried out on the functional effects of these mutations in order to evaluate their effect on viral evolution and functional immunity. Future outbreaks and the virus’s capability to jump to new human targets can be approximated from such mutations. Phylogenetic Analysis The phylogenetic analysis of MPXV discussed in this work sheds important light on the virus's genetic and structural changes, essential for knowing its molecular characteristics, epidemiology, and potential treatments. These findings are commensurate with and supplement prior work on MPXV strains and their phylogenetic relationship with the variola virus. We adopted the BLAST algorithm to search for MPXV sequences from existing databases, which provides an implicit alignment, crucial in developing a phylogenetic tree Patrono et al. [ 90 ]. This strategy is similar to that in the earlier works, including those of et al. [ 86 ], who used sequence comparison to analyze the genetic variability of MPXV strains and its relative variola virus that causes smallpox. Diaz [ 91 ] described the phylogenetic analysis of MPXV with variola to establish computer simulations and show that they both originated from a single progenitor virus. A similar idea is reflected in our phylogenetic tree (Fig. 7 ) and data from previous works where both viruses diverged several thousand years ago and acquired similar biology and life cycles. Fig. 7. Open in a new tab Unraveling the Phylogenetic Diversity of MPXV : A Regional Analysis of Genetic Variations However, our study goes further, as it reveals that MPXV remains a severe threat to public health, as opposed to smallpox, which no longer exists. Such consideration underlines the necessity of further investigations concerning the genetic constitution of MPXV to identify specific strategies to counteract the virus. The results identified here, especially if one considers can highlight the genetic features that might potentially be instrumental in deciphering the implications of the variability within different MPXV strains in terms of their broad tropism and pathogenicity, the subject of more recent work by Davis et al. [ 92 ]. Following the initial phylogenetic analysis performed by Atasoy et al. [ 89 ], their recent study also depicted a robust genetic variation at the MPXV strain level. This variation may be pivotal in influencing transmission rates and disease presentation. These data corroborate our previous work to some extent, where we identified distinct genomic regions in MPXV , and some of them may have increased pathogenicity or tropism. For instance et al. [ 90 ] indicate that some MPXV strains, including those from Central and West Africa, show higher mutation rates, implying that they may challenge the virus's propensity to infect diverse animal species or adapt to novel human host populations. This emphasises the need for the constant surveillance of genetic changes in MPXV strains, where we discuss several phylogenetic groups that might be associated with different epidemiological profiles of recent outbreaks Roper et al. [ 93 ]. This agrees with recent studies, and our work adds further evidence by showing that genetic variation within MPXV strains is central to their biology and ability to re-emerge as zoonotic pathogens. As illustrated in Fig. 8 , these variations, concentrating on the genetic and structural differences of MPXV from other virus strains, could determine the virus's capacity to escape immune action or resist existing antiviral treatments. This aspect is especially crucial given more recent work like Roper et al. [ 93 ] that encouraged the enhancement of diagnosis approaches and existing and new vaccines to consider these variations. Fig. 8. Open in a new tab Exploring Genetic and Structural Variations of MPXV and its Comparison with Other Viruses Domain and Motif Analysis In the context of the MPXV domain, various genes and their symbols are used to identify specific genetic information about the virus, as shown in Fig. 9 . These genes and their symbols are typically used in databases such as GenBank, NCBI, and UniProt, which store and catalog genomic information about various organisms, including viruses. One example of a gene associated with the MPXV is the hemagglutinin (HA) gene, which encodes a protein involved in the virus's ability to infect and spread between cells. Its gene symbol in the NCBI database is “POXVHA”. Another example is the thymidine kinase (TK) gene, which encodes an enzyme in virus replication. Its gene symbol in the NCBI database is “POXTK”. Many other genes and proteins are associated with the MPXV and play essential roles in the virus's biology and pathogenesis. Studying these genes and their functions is a critical component of the MPXV domain, as it provides insight into the virus and its potential for causing disease. Fig. 9. Open in a new tab Overview and representation of MPXV Domains Pharmacological Analysis and Clinical Trials In MPXV treatment, ongoing clinical trials explore antiviral drugs, immunomodulators, and supportive care strategies to mitigate the disease's impact, with promising early results in some cases. MPXV Treatment: FDA-Approved Drugs There is still no effective antiviral medication for MPXV with a remedy directed at supportive therapies that may be employed to relieve the patient’s signs and symptoms and prevent complications [ 7 , 94 ]. Tecovirimat (TPOXX) antiviral smallpox was approved for MPXV under the Expanded Access Investigational New Drug (EA-IND) and is not readily available for use Johri et al. [ 95 ]. Moreover, several drugs have been evaluated in vitro and in vivo against MPXV, including another adenine nucleoside, cidofovir (Vistide), and a DNA polymerase inhibitor, brincidofovir (Tembexa); however, the clinical efficacy of these drugs in humans has not been confirmed yet, and further studies are needed [ 96 ]. For MPXV , vaccinia immune globulin intravenous (VIGIV), usually applied for complications of smallpox, is used; nonetheless, there is a limited amount of evidence available [ 98 ]. Gieryńska et al. [ 97 ]and Upadhayay et al. [ 98 ] have recently published supportive data for these treatments. However, the authors stress the necessity of further research into the effectiveness of these treatments for MPXV [ 48 , 99 ]. In addition, Lanier et al. [ 100 ] also pointed out the need to conduct extensive clinical trials to evaluate the safety and effectiveness of these drugs for MPXV treatment. Although these drugs showed antiviral properties against MPXV , none have been approved by the FDA for the treatment of the disease, and usage is still minimal and monitored by a physician. Hence, there is a need to continue looking for and laying out more controlled trials that best define the efficient treatment approaches in managing MPXV . Current Status of Monkeypox Vaccine and Clinical Trials Monkeypox is a viral disease that primarily affects humans and other primates. It is caused by the MPXV and is characterized by fever, skin rash, and other symptoms similar to smallpox [ 101 ]. Currently, two vaccines are used for monkeypox prevention in the U.S.: JYNNEOS and ACAM2000. JYNNEOS, approved by the FDA for both smallpox and monkeypox, is administered in two doses and has a lower risk profile, making it suitable for immunocompromised individuals. ACAM2000, primarily for smallpox but used for monkeypox under an expanded access protocol, requires a single dose with multiple injections but is associated with higher risks. Vaccination can be applied as pre-exposure prophylaxis (PrEP) to prevent future infections or post-exposure prophylaxis (PEP) to mitigate the severity of the disease if administered within 4 days of exposure or up to 14 days to reduce symptoms. The CDC also employs PEP++ for those at increased risk of exposure. Currently, eight registered studies on ClinicalTrials.gov are investigating various aspects of monkeypox, including the safety and efficacy of vaccines like IMVAMUNE®, ST-246, and MVA vaccines (IMVANEX® and JYNNEOS®), as well as the potential of tecovirimat, an antiviral drug as detail presented in Table 4 . Table 4. MPXV Vaccine Development: Current Status and Latest Clinical Trials Number Research Mode of research Design of research Country Interventions Outcome Measures NCT05476744 Viral Clearance and Epidemiological Characteristics Observational Cohort, Prospective Spain N/A Viral clearance in skin lesions, blood, and oropharyngeal swabs NCT05443867 MPXV Symptomatic Shedding Observational Cohort, Prospective Belgium N/A Secondary attack rate of MPXV infection and seroconversion NCT05438953 Contact at Risk of MPXV Infection Interventional Non-randomized, Open Label France MVA vaccine (IMVANEX® and JYNNEOS®) Proportion of failure of MVA vaccine and early vaccine immunogenicity NCT02977715 IMVAMUNE® Smallpox Vaccine in Adult Healthcare Personnel Interventional Single Group, Open Label DRC IMVAMUNE® The proportion of participants with suspected or confirmed MPXV infection and orthopoxvirus antibody responses NCT05058898 A One Health Study of MPXV Human Infection Observational Case–Control, Prospective Central African Republic Blood samples, scabs, and pus samples Proportion of MPXV cases and effective reproduction rate (R) NCT03745131 Cohort Study of Healthcare Workers Receiving Imvanex® Observational Cohort, Prospective United Kingdom Blood draw Antibody responses to Imvanex® NCT02080767 Tecovirimat (ST-246) Treatment for Orthopox Virus Exposure Expanded Access N/A N/A Tecovirimat N/A NCT00728689 Phase I Trial of an Investigational Smallpox Medication Interventional Randomised, Crossover, Triple Masking United States ST-246 Days 1–3 Pharmacokinetic parameters for ST-246 Open in a new tab Ethnobotanical Analysis of MPXV Ethnobotanical analysis of MPXV explores the traditional knowledge and use of plants in preventing or treating the disease within indigenous communities. This investigation delves into the plants' medicinal properties, their preparation methods, and the cultural significance associated with their use. Ethnobotanical research sheds light on potential herbal remedies or preventive measures passed down through generations, contributing to a broader understanding of MPXV management and prevention strategies. Plant-Based Treatments for MPXV : A Promising Alternative Herbal treatments of MPXV are seemingly distinct from synthetic drugs and animal-based vaccines as they derive natural products with antiviral properties to treat MPXV infection as in Table 5 . For instance, Vernonia amygdalina , which is used in the treatment of malaria, is known to have effectiveness in minimizing the severity of MPXV infections, other compounds obtained from plants, like flavonoids from fruits, vegetables, and medicinal plants, have been shown to possess antiviral properties (Dixit et al., 2020). These plant products are commendable for their low price, ease of processing, fewer complications, and cultural heritage of centuries-enduring folk use [ 102 ]. Consequently, there remains a compelling need to define the right dosage, mode of delivery, and possible interaction with other drugs. An excellent example of microtubules that are crucial for cell division and viral replication is also practical for antiviral treatment, and chemicals like colchicine [ 103 ], which comes from the autumn crocus plant, will have antiviral activity against HPV and herpes simplex [ 104 ]. The same goes for vinblastine and vincristine derived from annual and perennial vinca plants and paclitaxel that belongs to taxane plants; they are also used in cancer chemotherapy and are effective against HIV and hepatitis B and C [ 105 ]. The latest research showed that microtubule-targeting agents can suppress variola virus replication, related to the MXPV. However, further studies are needed to assess the efficacy of these reagents in treating MPXV [ 106 ]. Table 5. Plant-based treatments for MPXV : a promising alternative Plant-based treatment Potential benefits Recommended dosage Precautions References Vitamin C supplements Boosts the immune system and reduces inflammation 500-1000 mg, 3–4 times daily High doses can cause diarrhea and other digestive issues [ 107 ] Echinacea supplements It enhances the immune system and may help reduce symptoms of infection Follow label instructions, typically 500–1000 mg daily It may interact with certain medications, including immunosuppressants [ 108 ] Elderberry supplements Antiviral properties may help reduce symptoms of infection Follow label instructions, typically 500–1000 mg daily It may interact with certain medications, including immunosuppressants. Consult a healthcare professional for personalized advice [ 109 ] Astragalus supplements Boosts the immune system and may help reduce symptoms of infection Follow label instructions, typically 500–1000 mg daily It may interact with certain medications, including immunosuppressants [ 110 ] Andrographis supplements Antiviral properties may help reduce symptoms of infection Follow label instructions, typically 500–1000 mg daily It may interact with certain medications, including immunosuppressants [ 111 ] Licorice root supplements Anti-inflammatory properties may help reduce symptoms of infection Follow label instructions, typically 500–1000 mg daily High doses can cause potassium loss, high blood pressure, and other health issues [ 112 ] Open in a new tab Similarly, several research works done on different medicinal plants like Azadirachta indica and Opuntia streptacantha reported the antiviral activity against DNA viruses; therefore, extracts from these medicinal plants might also be worthy for MPXV cure [ 106 ]. The healing effect of plant extracts is not doubtful; however, as it is known, some of the compounds may have toxic effects [ 113 ], so their use for the treatment of MPXV needs thorough testing as well as laboratory and clinical trials. Recent work also stipulates that, while plant-based remedies may have traditional application, detailed controlled trials are needed to assess their potential as MPXV treatments [ 55 ]. MPXV Prevention and Control Preventing and controlling MPXV involves a multifaceted approach, including public education, surveillance, and rapid response. These measures aim to minimize transmission, isolate infected individuals, and engage communities in outbreak containment. Early detection, quarantine, and international collaboration are vital to practical MPXV prevention and control efforts. Preventing the Spread of MPXV Virus: Tips and Recommendations Preventing the spread of MPXV involves several methods, as mentioned in Table 6 . First and foremost, individuals should be vaccinated against the disease if they live in or travel to areas where MPXV is common[ 114 ]. The vaccine is not 100% effective, but it can reduce the severity of symptoms and lower the risk of contracting the virus. Additionally, individuals should take precautions to avoid contact with infected animals, as they are the primary source of the virus. This includes avoiding direct contact with infected animals or their bodily fluids, and thoroughly cooking meat before consumption. Washing hands frequently, particularly after handling any animal products or after being in contact with infected individuals, can also help prevent the spread of the virus. It is also important to avoid close contact with individuals infected with MPXV , as the virus is highly contagious and can spread from person to person. If an individual becomes infected, it is crucial to seek medical attention immediately to receive appropriate treatment and reduce the spread of the virus to others. Table 6. Prevention method of MPXV virus Prevention method Details References Awareness and education A primary prevention strategy involves raising awareness about risk factors and educating people about measures to reduce exposure to the virus [ 115 ] Vaccination Scientific studies are underway to assess the feasibility and appropriateness of vaccination to prevent and control MPXV . Some countries offer vaccines to those at risk, such as laboratory personnel, rapid response teams, and health workers [ 116 , 117 ] Reducing human-to-human transmission Surveillance and rapid identification of new cases to prevent and control are critical for outbreak containment. Health workers and household members are at higher risk and should implement standard infection control precautions [ 117 ] Reducing zoonotic transmission Avoid unprotected contact with wild animals, incredibly sick or dead animals and their meat, blood, and other parts. Cooking all foods containing animal meat or parts thoroughly before eating [ 118 ] Restrictions on animal trade Some countries have regulations restricting the importation of rodents and non-human primates. Captive animals potentially infected with MPXV should be isolated and placed in quarantine [ 119 ] Isolation and quarantine A person with an MPXV infection should wear a mask and avoid close contact with others until the skin lesions are completely healed, which can take up to two weeks. If exposed, contact a physician or public health department [ 20 ] Protection during sexual contact Avoid close contact with others and have protected sexual contact to reduce the risk of transmission [ 120 ] Early identification and treatment Surveillance and rapid identification of new cases are critical for outbreak containment. If you have been exposed to MPXV, please contact your physician or public health department [ 121 ] Standard infection control Health workers caring for patients with suspected or confirmed MPXV virus infection should implement standard infection control precautions [ 122 ] Cooking food thoroughly All foods containing animal meat or parts must be thoroughly cooked before eating [ 123 ] Avoidance of unprotected contact with wild animals Unprotected contact with wild animals, especially those that are sick or dead, including their meat, blood, and other parts, must be avoided [ 124 ] Restrictions on animal trade Some countries have regulations restricting the importation of rodents and non-human primates. Any potentially infected animals should be isolated and placed in quarantine [ 124 ] Open in a new tab AI/ML-Based Treatments in Managing MPXV AI and ML can be game changers for Monkeypox (MPX) regarding how new detection methods could be implemented, forecasts could be made, therapeutic approaches could be best implemented, and funding could be used effectively. Dermatological images of early MPX can also be diagnosed using high accuracy with deep learning models and AI algorithms, according to the study by Almufareh. Furthermore, using the current data feed and the environment, AI is more capable of modeling MPX than any standard epidemic models [ 125 , 126 ]. Regarding management, extensive data analysis and artificial intelligence drug repositioning approaches have brought numerous suspect antiviral molecules for MPX, thereby expediting efforts to find reasonable treatment (Wang et al., 2023). Another application uses AI models to forecast hospital bed occupancy and personnel requirements FatehiJananloo et al. [ 127 ]. While some prior work in this field used more classical epidemiological approaches, AI produces more timely and accurate analyses of an outbreak. However, there are still issues with healthcare data security and adding AI to existing health systems. However, these challenges should be surprisingly viewed as opportunities because of the AI models’ growing precision and real-time implementation, which forward faster and more effective approaches to managing MPX outbreaks than the traditional methods [ 128 ]. Research Potentials Our research holds the potential to significantly enhance our understanding of the MPXV , its genetic characteristics, and evolutionary patterns. This knowledge can inform more effective disease surveillance, diagnosis, and intervention strategies, ultimately reducing transmission and morbidity and potentially preventing it from becoming a global health threat. Our emphasis on integrating advanced technologies and data analysis techniques also underscores the potential for innovative approaches to address emerging infectious diseases beyond MPXV . Future Prospective Our research prospects include continued exploration of MPXV genetics and its impact on public health. This research can lead to improved diagnostics, treatments, and preventive measures. Our emphasis on advanced technologies and data integration also paves the way for more agile responses to emerging infectious diseases, offering a blueprint for future pandemic preparedness and response efforts. Ultimately, our work has the potential to enhance global health resilience and reduce the impact of infectious disease outbreaks. Conclusion MPXV is a zoonotic disease caused by the MPXV and is a potential public health threat. Our comprehensive study of the MPXV has provided valuable insights into its genetic makeup, evolutionary dynamics, and possible implications for public health. Through genomic analysis, mutation screening, phylogenetics, comparative genomics, and molecular analysis, we have highlighted the importance of timely disease surveillance, standardized gene nomenclature within the Ortho-poxvirus genus, and ongoing research into genetic mutations. We have also emphasized the distinct biology of MPXV compared to the variola virus and advanced technologies' critical role in addressing emerging infectious diseases. Our findings have implications for disease surveillance, diagnostics, treatments, and prevention strategies, underscoring the need for continued research and preparedness in the face of evolving viral threats and integrating epidemiological and genomic data in real-time aids in informed public health decisions, averting the potential global threat of MPXV through effective prevention and control measures. Acknowledgements The authors acknowledge the generous support from the Researchers Supporting Project Number (RSPD2025R713) King Saud University, Riyadh, Saudi Arabia. Author’s contribution In this comprehensive genomic study of the MPXV virus among different countries, Imran Zafar and Rohit Sharma served as lead investigators, overseeing the research process and ensuring the quality of the study. Faheem Kanwal led the mutation screening analysis, while Muhammad Azmat conducted the phylogenetic analysis. Ahsanullah Unar contributed to data collection and processing, while Ijaz Ali conducted laboratory experiments. Waqas Yousaf assisted in bioinformatics analysis and data visualization, and Qurat ul Ain conducted a literature review and manuscript editing. Mohd Ashraf Rather contributed to the epidemiological study, and Nemat Ali, Mohammad Rashid Khan, and Amandeep Singh provided technical support and manuscript review. Each author played a significant role in their respective areas, from data analysis to manuscript preparation, contributing to the comprehensiveness and quality of the study. Declarations Conflict of interest The authors declare no conflict of interest. Footnotes Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Contributor Information Imran Zafar, Email: Bioinfo.pk@gmail.com. Rohit Sharma, Email: rohitsharma@bhu.ac.in. References 1. Bunge EM et al (2022) The changing epidemiology of human monkeypox—A potential threat? A systematic review. PLoS Negl Trop Dis 16:e0010141 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 2. Altindis M, Puca E, Shapo L (2022) Diagnosis of monkeypox virus–an overview. Travel Med Infect Dis 50:102459 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 3. Elsayed S, Bondy L, Hanage WP (2022) Monkeypox virus infections in humans. Clin Microbiol Rev 35:e00092-e122 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 4. Chan-Tack KM et al (2019) Assessing a drug for an eradicated human disease: US Food and Drug Administration review of tecovirimat for the treatment of smallpox. Lancet Infect Dis 19:e221–e224 [ DOI ] [ PubMed ] [ Google Scholar ] 5. Farahat RA et al (2022) Human monkeypox disease (MPX). Infez Med 30:372–391 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 6. Sasidharanpillai S (2022) Monkeypox: an update. J Skin Sex Transm Dis 4:149 [ Google Scholar ] 7. Kaler J, Hussain A, Flores G, Kheiri S, Desrosiers D (2022) Monkeypox: a comprehensive review of transmission, pathogenesis, and manifestation. Cureus 14:e26531 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 8. Kumar N, Acharya A, Gendelman HE, Byrareddy SN (2022) The 2022 outbreak and the pathobiology of the monkeypox virus. J Autoimmun 131:102855 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 9. Silva NIO, de Oliveira JS, Kroon EG, Trindade GDS, Drumond BP (2020) Here, there, and everywhere: the wide host range and geographic distribution of zoonotic orthopoxviruses. Viruses 13:43 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 10. Luna N et al (2022) Phylogenomic analysis of the monkeypox virus (MPXV) 2022 outbreak: Emergence of a novel viral lineage? Travel Med Infect Dis 49:102402 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 11. Musa SS et al (2022) Transmission dynamics of monkeypox virus in Nigeria during the current COVID-19 pandemic and estimation of effective reproduction number. Vaccines 10:2153 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 12. Mazzoccoli G, Vinciguerra M, Carbone A, Relógio A (2020) The circadian clock, the immune system, and viral infections: the intricate relationship between biological time and host-virus interaction. Pathogens 9:83 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 13. Lossi L (2022) The concept of intrinsic versus extrinsic apoptosis. Biochem J 479:357–384 [ DOI ] [ PubMed ] [ Google Scholar ] 14. Beer EM, Rao VB (2019) A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy. PLoS Negl Trop Dis 13:e0007791 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 15. Minhaj FS et al (2022) Monkeypox outbreak—nine states, May 2022. Morb Mortal Wkly Rep 71:764 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 16. Girometti N et al (2022) Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis. Lancet Infect Dis 22:1321–1328 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 17. Vaughan A et al (2018) Two cases of monkeypox imported to the United Kingdom, September 2018. Eurosurveillance 23:1800509 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 18. King NJ, Hewitt J, Perchec-Merien A-M (2018) Hiding in plain sight? It’s time to investigate other possible transmission routes for hepatitis E virus (HEV) in developed countries. Food Environ Virol 10:225–252 [ DOI ] [ PubMed ] [ Google Scholar ] 19. Petrakis D et al (2020) Obesity-a risk factor for increased COVID-19 prevalence, severity and lethality. Mol Med Rep 22:9–19 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 20. Gomez-Lucia E (2022) Monkeypox: some keys to understand this emerging disease. Animals 12:2190 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 21. Abdelaal A et al (2022) Preventing the next pandemic: is live vaccine efficacious against monkeypox, or is there a need for killed virus and mRNA vaccines? Vaccines 10:1419 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 22. Tewari M, Rana P, Pande V (2024) Nanomaterial-based biosensors for the detection of COVID-19. Indian J Microbiol 24:1–17 [ DOI ] [ PMC free article ] [ PubMed ] 23. Kim H et al (2020) Antibody responses to SARS-CoV-2 antigens in humans and animals. Vaccines 8:684 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 24. Liu M et al (2020) Use of personal protective equipment against coronavirus disease 2019 by healthcare professionals in Wuhan, China: cross sectional study. BMJ 369:m2195 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 25. Anwar MZ et al (2022) COVID-MVP: an interactive visualization for tracking SARS-CoV-2 mutations, variants, and prevalence, enabled by curated functional annotations and portable genomics workflow. bioRxiv, p. 2022.06. 07.493653 26. Saraiva GL, Vidigal PMP, Fietto JLR, Bressan GC, Silva Júnior A, de Almeida MR (2018) Evolutionary analysis of Porcine circovirus 3 (PCV3) indicates an ancient origin for its current strains and a worldwide dispersion. Virus Genes 54:376–384 [ DOI ] [ PubMed ] [ Google Scholar ] 27. Canakoglu A, Pinoli P, Bernasconi A, Alfonsi T, Melidis DP, Ceri S (2021) ViruSurf: an integrated database to investigate viral sequences. Nucleic Acids Res 49:D817–D824 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 28. Marriam S et al (2023) Elucidation of novel compounds and epitope-based peptide vaccine design against C30 endopeptidase regions of SARS-CoV-2 using immunoinformatics approaches. Front Cell Infect Microbiol 13:1134802 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 29. Ali S et al (2023) Predicting the effects of rare genetic variants on oncogenic signaling pathways: A computational analysis of HRAS protein function. Front Chem 11:1173624 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 30. Marriam S et al (2020) Designing a potential multi-epitopes based vaccine against SARS-CoV-2 targeting C30 endopeptidase regions using immunoinformatics approaches. J Biomol Struct Dyn 13:568 [ Google Scholar ] 31. Zafar I et al (2022) Genome-wide identification and analysis of GRF (growth-regulating factor) gene family in Camila sativa through in silico approaches. J King Saud Univ Sci 34:102038 [ Google Scholar ] 32. Zafar I, Iftikhar R, Ahmad SU, Rather MA (2021) Genome wide identification, phylogeny, and synteny analysis of sox gene family in common carp (Cyprinus carpio). Biotechnol Rep 30:e00607 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 33. Zafar I et al (2021) Roles of bioinformatics in reproductive science. In: Recent updates in molecular endocrinology and reproductive physiology of fish. Springer, pp 203–228 34. Rayan RA, Zafar I, Tsagkari C (2021) Blockchain technology for healthcare cloud-based data privacy and security. In Integr. WSNs into Internet of Things. CRC Press, pp 335–349 35. Rayan RA, Tsagkaris C, Zafar I, Moysidis DV, Papazoglou AS (2022) Big data analytics for health: a comprehensive review of techniques and applications. Big Data Anal Healthc 1:83–92 36. Rayan RA, Zafar I, Tsagkaris C (2021) Artificial Intelligence and Big Data Solutions for COVID-19. In: Intelligent data analysis for COVID-19 pandemic 2021. Springer, 115–127 37. Nunes PCG et al (2018) NS1 antigenemia and viraemia load: potential markers of progression to dengue fatal outcome? Viruses 10:326 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 38. Smiley JR, Chang KO, Hayes J, Vinjé J, Saif LJ (2002) Characterization of an enteropathogenic bovine calicivirus representing a potentially new calicivirus genus. J Virol 76:10089–10098 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 39. Sougrat R et al (2007) Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry. PLoS Pathog 3:e63 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 40. Forni D, Cagliani R, Molteni C, Clerici M, Sironi M (2022) Monkeypox virus: The changing facets of a zoonotic pathogen. Infect Genet Evol 105:105372 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 41. Quarleri J, Delpino MV, Galvan V (2022) Monkeypox: considerations for the understanding and containment of the current outbreak in non-endemic countries. Geroscience 44:2095–2103 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 42. Gelderblom HR, Madeley D (2018) Rapid viral diagnosis of orthopoxviruses by electron microscopy: optional or a must? Viruses 10:142 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 43. Okyay RA et al (2022) Another epidemic in the shadow of Covid 19 pandemic: a review of monkeypox. Proteins 7:10–14744 [ Google Scholar ] 44. Dasgupta G et al (2012) “Immunodominant ‘asymptomatic’ herpes simplex virus 1 and 2 protein antigens identified by probing whole-ORFome microarrays with serum antibodies from seropositive asymptomatic versus symptomatic individuals,” (in eng). J Virol 86:4358–4369 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 45. Reynolds SE (2016) Characterization of the cowpox and mousepox homologs of the smallpox virus B22 protein and their roles in mouse disease models. University of Maryland, College Park [ Google Scholar ] 46. Pinto AÁF (2022) Insights about the evolutionary mechanisms of poxviruses: Myxoma virus in Lepus, a case study 47. A. J. M. S. o. H. C. Bowie (2003) Modulation of Toll-like receptor signalling by viruses 62:109. 48. Huang Y et al (2024) Multi-omics characterization of the monkeypox virus infection. Nat Commun 15(1):6778 [ DOI ] [ PMC free article ] [ PubMed ] 49. Wilder-Smith A (2021) COVID-19 in comparison with other emerging viral diseases: risk of geographic spread via travel. Trop Dis Travel Med Vaccines 7:1–11 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 50. Saxena SK et al (2023) Re-emerging human monkeypox: a major public-health debacle. J Med Virol 95:e27902 [ DOI ] [ PubMed ] [ Google Scholar ] 51. Kasarla RR (2022) Human monkeypox: an emerging and neglected viral zoonosis of public health concern. J Univ Coll Med Sci 10:1–3 [ Google Scholar ] 52. Gessain A, Nakoune E, Yazdanpanah Y (2022) Monkeypox. N Engl J Med 387:1783–1793 [ DOI ] [ PubMed ] [ Google Scholar ] 53. Lai C-C, Hsu C-K, Yen M-Y, Lee P-I, Ko W-C, Hsueh P-R (2022) Monkeypox: an emerging global threat during the COVID-19 pandemic. J Microbiol Immunol Infect 55:787–794 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 54. Sah R et al (2022) Monkeypox and its possible sexual transmission: where are we now with its evidence? Pathogens 11:924 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 55. Warner BM et al (2022) In vitro and in vivo efficacy of Tecovirimat against a recently emerged 2022 Monkeypox virus isolate. Sci Transl Med 14:eade7646 [ DOI ] [ PubMed ] [ Google Scholar ] 56. Abdelaal A, Serhan HA, Mahmoud MA, Rodriguez-Morales AJ, Sah R (2022) Ophthalmic manifestations of monkeypox virus. Eye 22:1–3 [ DOI ] [ PMC free article ] [ PubMed ] 57. Hammerschlag Y et al (2022) Monkeypox infection presenting as genital rash, Australia, May 2022. Eurosurveillance 27:2200411 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 58. Meo S, Klonoff D (2022) Human monkeypox outbreak: global prevalence and biological, epidemiological and clinical characteristics-observational analysis between 1970–2022. Eur Rev Med Pharmacol Sci 26:5624–5632 [ DOI ] [ PubMed ] [ Google Scholar ] 59. Patel M, Surti M, Adnan M (2022) Artificial intelligence (AI) in Monkeypox infection prevention. J Biomol Struct Dyn 1–5 [ DOI ] [ PMC free article ] [ PubMed ] 60. Almutairi SA (2022) DL-MDF-OH2: optimized deep learning-based monkeypox diagnostic framework using the metaheuristic harris hawks optimizer algorithm. Electronics 11:4077 [ Google Scholar ] 61. Ahsan MM et al (2023) Deep transfer learning approaches for Monkeypox disease diagnosis. Expert Syst Appl 216:119483 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 62. Mandal AK, Sarma PKD, Dehuri S (2023) Machine learning approaches and particle swarm optimization based clustering for the human monkeypox viruses: a study. In Innovations in intelligent computing and communication: first international conference, ICIICC 2022, Bhubaneswar, Odisha, India, December 16–17, 2022, Proceedings, 2023, Springer. pp 313–332 63. Alakus TB, Baykara M (2022) Comparison of monkeypox and wart DNA sequences with deep learning model. Appl Sci 12:10216 [ Google Scholar ] 64. Vandenbogaert M et al (2022) Nanopore sequencing of a monkeypox virus strain isolated from a pustular lesion in the Central African Republic. Sci Rep 12:10768 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 65. Tang Z et al (2022) A bioinformatics approach to systematically analyze the molecular patterns of monkeypox virus-host cell interactions. bioRxiv, p. 2022.10. 12.511850 [ DOI ] [ PMC free article ] [ PubMed ] 66. Muth T (2022) Setting up the bioinformatics environment for employing meta-omics techniques in microbiome research and pathogen diagnostics 67. Bhattacharya M, Chatterjee S, Nag S, Dhama K, Chakraborty C (2022) Designing, characterization, and immune stimulation of a novel multi-epitopic peptide-based potential vaccine candidate against monkeypox virus through screening its whole genome encoded proteins: an immunoinformatics approach. Travel Med Infect Dis 50:102481 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 68. Rokni M, Ghasemi V, Tavakoli Z (2020) Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: comparison with SARS and MERS. Rev Med Virol 30:e2107 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 69. Lal A, Ashworth HC, Dada S, Hoemeke L, Tambo E (2022) Optimizing pandemic preparedness and response through health information systems: lessons learned from Ebola to COVID-19. Disaster Med Public Health Prep 16:333–340 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 70. Kangabam R et al (2021) Next-generation computational tools and resources for coronavirus research: from detection to vaccine discovery. Comput Biol Med 128:104158 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 71. Mishra S et al (2022) An immunoinformatic approach towards development of a potent and effective multi-epitope vaccine against monkeypox virus (MPXV). J Biomol Struct Dyn 1–14 [ DOI ] [ PubMed ] 72. Sena-Esteves M, Gao G (2020) Introducing genes into mammalian cells: viral vectors. Cold Spring Harbor Protoc 2020:pdb-top095513 [ DOI ] [ PubMed ] [ Google Scholar ] 73. Rahman MJ (2020) Cascade poxvirus evolution involving retrotransposon-mediated host gene capture, complementation and recombination. University of California, Davis [ Google Scholar ] 74. Patel R, Shaikh A, Marathe A (2023) "Incidence of secondary blood stream infections in Covid 19 (SARS-nCoV II) patients. Indian J Microbiol Res 8:128–131 [ Google Scholar ] 75. Sharma V, Aggarwal D, Sharma A (2022) An overview on monkeypox, current paradigms and advances in its vaccination, treatment and clinical management: trends, scope, promise and challenges. J Pure Appl Microbiol 16:3000–3012 [ Google Scholar ] 76. Hiffler L, Rakotoambinina B (2020) Selenium and RNA virus interactions: potential implications for SARS-CoV-2 infection (COVID-19). Front Nutr 7:164 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 77. De Benedictis P, Leopardi S, Markotter W, Velasco-Villa A (2022) The importance of accurate host species identification in the framework of rabies surveillance, control and elimination. Viruses 14:492 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 78. Guo X et al (2022) Restriction-assembly: a solution to construct novel adenovirus vector. Viruses 14:546 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 79. Pecori R, Di Giorgio S, Paulo Lorenzo J, Nina Papavasiliou F (2022) Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination. Nat Rev Genet 23:505–518 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 80. Atyeo N, Papp B (2022) The ORF45 protein of kaposi’s sarcoma-associated herpesvirus and its critical role in the viral life cycle. Viruses 14:2010 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 81. Ahmad SU et al (2022) A comprehensive genomic study, mutation screening, phylogenetic and statistical analysis of SARS-CoV-2 and its variant omicron among different countries. J Infect Public Health 15:878–891 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 82. Bakhshandeh B et al (2021) Mutations in SARS-CoV-2; Consequences in structure, function, and pathogenicity of the virus. Microb Pathog 154:104831 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 83. Borzooee F, Asgharpour M, Quinlan E, Grant MD, Larijani M (2018) Viral subversion of APOBEC3s: lessons for anti-tumor immunity and tumor immunotherapy. Int Rev Immunol 37:151–164 [ DOI ] [ PubMed ] [ Google Scholar ] 84. Bécares M et al (2023) ISG15 is required for the dissemination of Vaccinia virus extracellular virions. Microbiol Spectrum 11:e04508-e4522 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 85. Jiang L et al (2024) A review of Mpox: biological characteristics, epidemiology, clinical features, diagnosis, treatment, and prevention strategies. In: Exploration, Wiley Online Library, p 20230112 [ DOI ] [ PMC free article ] [ PubMed ] 86. Yu X, Shi H, Cheng GJV (2023) "Mpox virus: its molecular evolution and potential impact on viral epidemiology. Viruses 15:995 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 87. Wang J et al (2024) Decoding and unravelling mpox, herpes, and syphilis infections: a state of art review. Curr Pharm Biotechnol. 10.2174/0113892010293479240709074020 [ DOI ] [ PubMed ] [ Google Scholar ] 88. González-Paz L et al (2023) Thermodynamics and conformational dynamics of primer nucleotide sequences associated with Monkeypox Virus (MpxV): comparative analysis of stability and specificity with a biophysical-computational approach. Biointerface Res Appl Chem 13:435 [ Google Scholar ] 89. Shahriar S (2022) Identifying the origin and mechanisms of pathological angiogenesis in neuroinflammatory diseases. Columbia University, New York [ Google Scholar ] 90. Patrono LV et al (2020) Monkeypox virus emergence in wild chimpanzees reveals distinct clinical outcomes and viral diversity. Nat Microbiol 5:955–965 [ DOI ] [ PubMed ] [ Google Scholar ] 91. Diaz JH (2021) The disease ecology, epidemiology, clinical manifestations, management, prevention, and control of increasing human infections with animal orthopoxviruses. Wilderness Environ Med 32:528–536 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 92. Davis C et al (2023) Temperature elevation synergises with and enhances the type-I IFN-mediated restriction of MPXV. BioRxiv. 10.1101/2023.09.29.56010638187557 [ Google Scholar ] 93. Roper RL et al (2023) "Monkeypox (Mpox) requires continued surveillance, vaccines, therapeutics and mitigating strategies. Vaccine 41:3171–3177 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 94. Luo Q, Han J (2022) Preparedness for a monkeypox outbreak. Infect Med 1:124–134 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 95. Johri N, Kumar D, Nagar P, Maurya A, Vengat M, Jain P (2022) Clinical manifestations of human monkeypox infection and implications for outbreak strategy. Health Sci Rev 5:100055 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 96. Soheili M, Nasseri S (2022) Monkeypox: virology, pathophysiology, clinical characteristics, epidemiology, vaccines, diagnosis, and treatments. J Pharm Pharm Sci 25:322–297 [ DOI ] [ PubMed ] [ Google Scholar ] 97. Gieryńska M et al (2023) Orthopoxvirus zoonoses—Do we still remember and are ready to fight? Pathogens 12:363 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 98. Upadhayay S et al (2022) Monkeypox infection: the past, present, and future. Int Immunopharmacol 113:109382 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 99. Alakunle E, Moens U, Nchinda G, Okeke MIJV (2020) Monkeypox virus in Nigeria: infection biology, epidemiology, and evolution. Viruses 12:1257 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 100. Lanier R et al (2010) Development of CMX001 for the treatment of poxvirus infections. Viruses 2:2740 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 101. Farasani A (2022) Monkeypox virus: future role in Human population. J Infect Public Health 15:1270–1275 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 102. Saikia S, Chetia P (2024) Antibiotics: from mechanism of action to resistance and beyond. Indian J Microbiol pp 1–25 [ DOI ] [ PMC free article ] [ PubMed ] 103. Ritter A, Kreis N-N (2022) Microtubule dynamics and cancer. Cancers 14:4368 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 104. Ullrich CI, Aloni R, Saeed ME, Ullrich W, Efferth TJP (2019) "Comparison between tumors in plants and human beings: Mechanisms of tumor development and therapy with secondary plant metabolites. Phytomedicine 64:153081 [ DOI ] [ PubMed ] [ Google Scholar ] 105. Abacha YZ (2020) Investigation of Nigerian Ethno-medicinal Plants as Potential Sources of Cytotoxic and Anti-plasmodial Compounds. Biological activity of Vitellaria paradoxa, Cyperus articulatus, Securidaca longepedunculata and semi-synthetic halogenated analogues of cryptolepine isolated from Cryptolepis sanguinolenta. University of Bradford 106. Hashim HO, Al-Shuhaib JM, Mohammed MK, Al-Shuhaib MBS (2024) Targeting monkeypox virus methyltransferase: virtual screening of natural compounds from middle-eastern medicinal plants 1:1–23 [ DOI ] [ PubMed ] 107. Hemilä H, Chalker E (2021) Commentary: Vitamin C supplementation for prevention and treatment of pneumonia. Front Med 7:595988 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 108. Aucoin M et al (2020) The effect of Echinacea spp. on the prevention or treatment of COVID-19 and other respiratory tract infections in humans: a rapid review. Adv Integr. Med. 7:203–217 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 109. Hawkins J, Baker C, Cherry L, Dunne E (2019) Black elderberry ( Sambucus nigra ) supplementation effectively treats upper respiratory symptoms: a meta-analysis of randomized, controlled clinical trials. Complement Ther Med 42:361–365 [ DOI ] [ PubMed ] [ Google Scholar ] 110. Liu J et al (2022) Evaluation of the effects of Astragalus polysaccharides as immunostimulants on the immune response of crucian carp and against SVCV in vitro and in vivo. Comp Biochem Physiol C Toxicol Pharmacol 253:109249 [ DOI ] [ PubMed ] [ Google Scholar ] 111. Jiang M et al (2021) Andrographis paniculata (Burm. f.) Nees and its major constituent andrographolide as potential antiviral agents. J Ethnopharmacol 272:113954 [ DOI ] [ PubMed ] [ Google Scholar ] 112. Hasan MK, Ara I, Mondal MSA, Kabir Y (2021) Phytochemistry, pharmacological activity, and potential health benefits of Glycyrrhiza glabra. Heliyon 7:e07240 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 113. Gezici S, Şekeroğlu N (2019) Current perspectives in the application of medicinal plants against cancer: novel therapeutic agents. Anti-Cancer Agents Med Chem (Formerly Current Medicinal Chemistry-Anti-Cancer Agents) 19:101–111 [ DOI ] [ PubMed ] [ Google Scholar ] 114. Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y (2022) Prevention and treatment of monkeypox. Drugs 82:957–963 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 115. Budreviciute A et al (2020) Management and prevention strategies for non-communicable diseases (NCDs) and their risk factors. Front Public Health 8:788 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 116. Chakraborty S et al (2022) Clinical management, antiviral drugs and immunotherapeutics for treating monkeypox. An update on current knowledge and futuristic prospects. Int J Surg (London, England) 105:106847 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 117. Thet AK et al (2022) The use of vaccinia immune globulin in the treatment of severe mpox virus infection in HIV/AIDS. Clin Infect Dis 76:1671–1673 [ DOI ] [ PubMed ] [ Google Scholar ] 118. De Clercq E (2021) Tribute to John C. Martin at the twentieth anniversary of the breakthrough of tenofovir in the treatment of HIV infections. Viruses 13:2410 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 119. Huston J, Curtis S, Egelund EF (2023) Brincidofovir: a novel agent for the treatment of smallpox. Ann Pharmacother. 10.1177/106002802311517 [ DOI ] [ PubMed ] [ Google Scholar ] 120. Chu DK et al (2020) Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. The lancet 395:1973–1987 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 121. Nuzzo JB, Borio LL, Gostin LO (2022) The WHO declaration of monkeypox as a global public health emergency. JAMA 328:615–617 [ DOI ] [ PubMed ] [ Google Scholar ] 122. Vaughan A et al (2020) Human-to-human transmission of monkeypox virus, United Kingdom, October 2018. Emerg Infect Dis 26:782 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 123. He J, Evans NM, Liu H, Shao S (2020) A review of research on plant-based meat alternatives: driving forces, history, manufacturing, and consumer attitudes. Compr. Rev. Food Sci. Food Saf. 19:2639–2656 [ DOI ] [ PubMed ] [ Google Scholar ] 124. Bukhari MH (2022) The truth of monkeypox outbreak: a guide for the diagnostic laboratories, health care workers and community in Pakistan. Biomedica 38:53–56 [ Google Scholar ] 125. Wankhade M, Rao ACS, Kulkarni CJ (2022) "A survey on sentiment analysis methods, applications, and challenges. Artif Intell Rev 55:5731–5780 [ Google Scholar ] 126. Ulukaya S, Sarıca AA, Erdem O, Karaali AJM (2023) MSCCov19Net: multi-branch deep learning model for COVID-19 detection from cough sounds. Med Biol Eng Comput 61:1619–1629 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 127. FatehiJananloo M, Stopps H, McArthur JJE (2024) Exploring artificial intelligence methods for energy prediction in healthcare Facilities: An In-Depth extended systematic review. Energy Build 320:114598 [ Google Scholar ] 128. Galanos V (2023) Expectations and expertise in artificial intelligence: specialist views and historical perspectives on conceptualisation, promise, and funding Articles from Indian Journal of Microbiology are provided here courtesy of Springer ACTIONS View on publisher site PDF (2.0 MB) Cite Collections Permalink RESOURCES Similar articles Cited by other articles Links to NCBI Databases Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top

Related documents

• Epidemiology and characteristics of cases with monkeypox virus clade I in the WHO European Region, 2024 to 2025.#298923
• Supporting Data for "Portable Detection of Monkeypox virus Clades using Bridging LAMP"#1090103
• Emergence and co-circulation of Monkeypox virus Clade Ia and Clade Ib in South Kivu, Democratic Republic of the Congo, January to May 2026#410896
• Diagnostic testing for the monkeypox virus (MPXV): interim guidance, 10 May 2024#324374
• Evaluation and comparison of three qPCR commercial assays and three automated platforms for the detection of monkeypox virus DNA#284287