Monkeypox Virus: Epidemiology, Virology, Diagnosis, Vaccine, and Therapeutics

Yunzheng Yan , Yaqin Sun , Guangyan Sun , Cheng Niu , Xinyuan Zhao , Ming Zhao , Tongyao Liu , Suyue Zhang , Hui Zhai , Ankang Liu , Shouzhi Yu , Shuyuan Pan , Wu Zhong , Yuntao Zhang , Song Li

MedComm ›› 2026, Vol. 7 ›› Issue (1) : e70525

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MedComm ›› 2026, Vol. 7 ›› Issue (1) :e70525 DOI: 10.1002/mco2.70525
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Monkeypox Virus: Epidemiology, Virology, Diagnosis, Vaccine, and Therapeutics
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Abstract

Since 2022, mpox epidemics have been sustaining and escalating over the world, posing a significant public health challenge. While significant progress has been made in diagnostic methodologies, prophylactic vaccines, and therapeutic interventions to mitigate monkeypox virus (MPXV) infection, scientific understanding of MPXV and related orthopoxviruses continues to evolve progressively. In order to keep pace with recent advancements, herein we review progress in mpox research from five key perspectives. This article first summarizes the latest epidemiological profiles, incorporating different viral lineages globally and in China, while highlighting their evolutionary history and distinct clinical characteristics. The virological profiles of MPXV shed light on its complete infectious lifecycle and the formation of distinct virus particle types. Clinically approved classical detection methods and emerging novel testing techniques are provided, establishing a framework for early diagnosis of mpox patients. The efficacy and safety of both licensed vaccines and those under development are analyzed to underscore their value in preventing mpox infection. Additionally, progress in approved and newly identified potential therapeutic agents is summarized and discussed, aiming to provide insights for further drug development and clinical treatment strategies.

Keywords

diagnosis / epidemiology / monkeypox virus / therapeutics / vaccine / virology

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Yunzheng Yan, Yaqin Sun, Guangyan Sun, Cheng Niu, Xinyuan Zhao, Ming Zhao, Tongyao Liu, Suyue Zhang, Hui Zhai, Ankang Liu, Shouzhi Yu, Shuyuan Pan, Wu Zhong, Yuntao Zhang, Song Li. Monkeypox Virus: Epidemiology, Virology, Diagnosis, Vaccine, and Therapeutics. MedComm, 2026, 7(1): e70525 DOI:10.1002/mco2.70525

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References

[1]

ICTV, “Virus Taxonomy,” 2024, https://ictv.global/taxonomy.

[2]

J. G. Rizk, G. Lippi, B. M. Henry, D. N. Forthal, and Y. Rizk, “Prevention and Treatment of Monkeypox,” Drugs 82, no. 9 (2022): 957–963.

[3]

A. Patel, J. Bilinska, J. C. H. Tam, et al., “Clinical Features and Novel Presentations of Human Monkeypox in a Central London Centre During the 2022 Outbreak: Descriptive Case Series,” BMJ 378 (2022): e072410.

[4]

Z. Jezek, M. Szczeniowski, K. M. Paluku, and M. Mutombo, “Human Monkeypox: Clinical Features of 282 Patients,” Journal of Infectious Diseases 156, no. 2 (1987): 293–298.

[5]

B. K. Titanji, A. Hazra, and J. Zucker, “Mpox Clinical Presentation, Diagnostic Approaches, and Treatment Strategies: A Review,” JAMA 332, no. 19 (2024): 1652–1662.

[6]

E. J. Tarín-Vicente, A. Alemany, M. Agud-Dios, et al., “Clinical Presentation and Virological Assessment of Confirmed Human Monkeypox Virus Cases in Spain: A Prospective Observational Cohort Study,” Lancet 400, no. 10353 (2022): 661–669.

[7]

S. K. Ahmed, M. G. Mohamed, E. A. Dabou, et al., “Monkeypox (Mpox) in Immunosuppressed Patients,” F1000Res 12 (2023): 127.

[8]

M. A. Islam, J. Mumin, M. M. Haque, et al., “Monkeypox Virus (MPXV): A Brief Account of Global Spread, Epidemiology, Virology, Clinical Features, Pathogenesis, and Therapeutic Interventions,” Infectious Medicine 2, no. 4 (2023): 262–272.

[9]

M. A. Islam. “Old Enemy With a New Face: Re-Emerging Monkeypox Disease—An Update,” 2022, https://microbiologyjournal.org/old-enemy-with-a-new-face-re-emerging-monkeypox-disease-an-update/.

[10]

M. A. Islam. “An Estimation of Five-Decade Long Monkeypox Case Fatality Rate: Systematic Review and Meta-Analysis,” 2022, https://helda.helsinki.fi/server/api/core/bitstreams/1e9a7836-da8b-4e36-8198-ecc452ad20a4/content.

[11]

A. Al-Musa, J. Chou, and B. LaBere, “The Resurgence of a Neglected Orthopoxvirus: Immunologic and Clinical Aspects of Monkeypox Virus Infections Over the Past Six Decades,” Clinical Immunology 243 (2022):109108.

[12]

M. E. DeWitt, C. Polk, J. Williamson, et al., “Global Monkeypox Case Hospitalisation Rates: A Rapid Systematic Review and Meta-analysis,” eClinicalMedicine 54 (2022): 101710.

[13]

WHO, “Mpox Outbreak,” 2024, https://www.who.int/emergencies/situations/mpox-outbreak.

[14]

WHO, “Monkeypox: Experts Give Virus Variants New Names,” 2022, https://www.who.int/news/item/12-08-2022-monkeypox–experts-give-virus-variants-new-names.

[15]

C. Happi, I. Adetifa, P. Mbala, et al., “Urgent Need for a Non-Discriminatory and Non-Stigmatizing Nomenclature for Monkeypox Virus,” PLoS Biology 20, no. 8 (2022): e3001769.

[16]

S. Soleimani and N. Motamed, “An Overview of Monkey Pox Disease as a Current Important Disease in the World,” Archives of Razi Institute 79, no. 6 (2024): 1121–1133.

[17]

H. Callaby, A. Belfield, A. D. Otter, et al., “Mpox: Current Knowledge and Understanding—A Scoping Review,” FEMS Microbiology Review 49 (2025): fuaf025.

[18]

K. M. Angelo, T. Smith, D. Camprubí-Ferrer, et al., “Epidemiological and Clinical Characteristics of Patients With Monkeypox in the GeoSentinel Network: A Cross-Sectional Study,” Lancet Infectious Diseases 23, no. 2 (2023): 196–206.

[19]

T. K. Suvvari, A. Ghosh, A. Lopinti, M. A. Islam, and P. Bhattacharya, “Hematological Manifestations of Monkeypox Virus (MPOX) and Impact of Human MPOX Disease on Blood Donation—What We Need to Know?,” New Microbes and New Infections 52 (2023): 101108.

[20]

I. Brosius, E. H. Vakaniaki, G. Mukari, et al., “Epidemiological and Clinical Features of Mpox During the Clade Ib Outbreak in South Kivu, Democratic Republic of the Congo: A Prospective Cohort Study,” Lancet 405, no. 10478 (2025): 547–559.

[21]

R. Hajjo, O. H. Abusara, D. A. Sabbah, and S. K. Bardaweel, “Advancing the Understanding and Management of Mpox: Insights Into Epidemiology, Disease Pathways, Prevention, and Therapeutic Strategies,” BMC Infectious Diseases [Electronic Resource] 25, no. 1 (2025): 529.

[22]

I. D. Ladnyj, P. Ziegler, and E. Kima, “A Human Infection Caused by Monkeypox Virus in Basankusu Territory, Democratic Republic of the Congo,” Bulletin of the World Health Organization 46, no. 5 (1972): 593–597.

[23]

WHO, “Global Mpox Trends,” 2025, https://worldhealthorg.shinyapps.io/mpx_global/#key-figures.

[24]

J. G. Breman, R. Kalisa, M. V. Steniowski, E. Zanotto, A. I. Gromyko, and I. Arita, “Human Monkeypox, 1970–79,” Bulletin of the World Health Organization 58, no. 2 (1980): 165–182.

[25]

Y. J. Hutin, R. J. Williams, P. Malfait, et al., “Outbreak of Human Monkeypox, Democratic Republic of Congo, 1996 to 1997,” Emerging Infectious Diseases 7, no. 3 (2001): 434–438.

[26]

CDC, “Human Monkeypox—Kasai Oriental, Democratic Republic of Congo, February 1996–October 1997,” 1997, https://www.cdc.gov/mmwr/preview/mmwrhtml/00050245.htm.

[27]

E. M. Bunge, B. Hoet, L. Chen, et al., “The Changing Epidemiology of Human Monkeypox-A Potential Threat? A Systematic Review,” PLOS Neglected Tropical Diseases 16, no. 2 (2022): e0010141.

[28]

E. R. Whitehouse, J. Bonwitt, C. M. Hughes, et al., “Clinical and Epidemiological Findings From Enhanced Monkeypox Surveillance in Tshuapa Province, Democratic Republic of the Congo During 2011–2015,” Journal of Infectious Diseases 223, no. 11 (2021): 1870–1878.

[29]

D. Ogoina, I. Damon, and E. Nakoune, “Clinical Review of Human Mpox,” Clinical Microbiology and Infection 29, no. 12 (2023): 1493–1501.

[30]

Centers for Disease Control and Prevention (CDC), “Multistate Outbreak of Monkeypox–Illinois, Indiana, and Wisconsin, 2003,” MMWR Morbidity and Mortality Weekly Report 52, no. 23 (2003):537–540.

[31]

K. D. Reed, J. W. Melski, M. B. Graham, et al., “The Detection of Monkeypox in Humans in the Western Hemisphere,” New England Journal of Medicine 350, no. 4 (2004): 342–350.

[32]

G. A. Shchelkunova and S. N. Shchelkunov, “Smallpox, Monkeypox and Other Human Orthopoxvirus Infections,” Viruses 15, no. 1 (2022): 103.

[33]

G. Andrei and R. Snoeck, “Differences in Pathogenicity Among the Mpox Virus Clades: Impact on Drug Discovery and Vaccine Development,” Trends in Pharmacological Sciences 44, no. 10 (2023): 719–739.

[34]

A. Yinka-Ogunleye, O. Aruna, M. Dalhat, et al., “Outbreak of Human Monkeypox in Nigeria in 2017–18: A Clinical and Epidemiological Report,” Lancet Infectious Diseases 19, no. 8 (2019): 872–879.

[35]

N. Ndodo, J. Ashcroft, K. Lewandowski, et al., “Distinct Monkeypox Virus Lineages Co-Circulating in Humans Before 2022,” Nature Medicine 29, no. 9 (2023): 2317–2324.

[36]

C. M. Gigante, B. Korber, M. H. Seabolt, et al., “Multiple Lineages of Monkeypox Virus Detected in the United States, 2021–2022,” Science 378, no. 6619 (2022): 560–565.

[37]

WHO, “WHO Director-General's Statement at the Press Conference Following IHR Emergency Committee Regarding the Multi-Country Outbreak of Monkeypox—23 July 2022,” 2022, https://www.who.int/director-general/speeches/detail/who-director-general-s-statement-on-the-press-conference-following-IHR-emergency-committee-regarding-the-multi–country-outbreak-of-monkeypox–23-july-2022.

[38]

WHO, “Surveillance, Case Investigation and Contact Tracing for Mpox (Monkeypox),” 2024, https://iris.who.int/bitstream/handle/10665/376306/WHO-MPX-Surveillance-2024.1-eng.pdf?sequence=1.

[39]

H. Adler, S. Gould, P. Hine, et al., “Clinical Features and Management of Human Monkeypox: A Retrospective Observational Study in the UK,” Lancet Infectious Diseases 22, no. 8 (2022): 1153–1162.

[40]

K. P. Saalbach, “Treatment and Vaccination for Smallpox and Monkeypox,” Advances in Experimental Medicine and Biology 1451 (2024):301–316.

[41]

M. N. Hasan, A. MohanaSundaram, P. Bhattacharya, and M. A. Islam, “Exploring the Relationship Between the Global Health Security Index and Monkeypox: An Analysis of Preparedness and Response Capacities,” Global Health 6 (2023): e0229.

[42]

WHO, “Mpox—African Region,” 2024, https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON528.

[43]

P. D. Katoto, W. Muttamba, E. Bahizire, et al., “Shifting Transmission Patterns of Human Mpox in South Kivu, DR Congo,” Lancet Infectious Diseases 24, no. 6 (2024): e354–e355.

[44]

A. Nizigiyimana, F. Ndikumwenayo, S. Houben, et al., “Epidemiological Analysis of Confirmed Mpox Cases, Burundi, 3 July to 9 September 2024,” Euro Surveillance 29, no. 42 (2024): 2400647.

[45]

J. H. McQuiston, R. Luce, D. M. Kazadi, et al., “U.S. Preparedness and Response to Increasing Clade I Mpox Cases in the Democratic Republic of the Congo—United States, 2024,” Mmwr Morbidity and Mortality Weekly Report 73, no. 19 (2024): 435–440.

[46]

WHO, “Fourth Meeting of the International Health Regulations (2005) Emergency Committee Regarding the Upsurge of Mpox 2024,” 2025, https://www.who.int/news/item/10-07-2025-fourth-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-upsurge-of-mpox-2024.

[47]

H. Zhao, W. Wang, L. Zhao, et al., “The First Imported Case of Monkeypox in the Mainland of China—Chongqing Municipality, China, September 16, 2022,” China CDC Weekly 4, no. 38 (2022): 853–854.

[48]

R. Ren, C. Li, W. Bai, et al., “The Epidemiological Characteristics of Mpox Cases—China, 2023,” China CDC Weekly 6, no. 26 (2024): 619–623.

[49]

H. Hu, Y. Zheng, L. Ruan, et al., “Clinical, Epidemiological, Virological Characteristics and Outcomes of 286 Patients Infected with Monkeypox Virus in China,” Allergy 80, no. 5 (2025): 1436–1451.

[50]

Y. Song, Y. Yan, J. Xu, et al., “Complete Genome Sequence Analysis of the First Imported Mpox Virus Clade Ib Variant in China,” Pathogens 14, no. 1 (2025): 102.

[51]

W. Pan, R. Ge, G. Zhu, et al., “The First Reported Case of Monkeypox Virus Clade Ib Infection in China-Clinical Presentation and Epidemiologic Implications,” International Journal of Infectious Diseases 155 (2025):107881.

[52]

D. Philpott, C. M. Hughes, K. A. Alroy, et al., “Epidemiologic and Clinical Characteristics of Monkeypox Cases—United States, May 17–July 22, 2022,” Mmwr Morbidity and Mortality Weekly Report 71, no. 32 (2022):1018–1022.

[53]

N. Girometti, R. Byrne, M. Bracchi, et al., “Demographic and Clinical Characteristics of Confirmed Human Monkeypox Virus Cases in Individuals Attending a Sexual Health Centre in London, UK: An Observational Analysis,” Lancet Infectious Diseases 22, no. 9 (2022): 1321–1328.

[54]

H. R. Gelderblom and D. Madeley, “Rapid Viral Diagnosis of Orthopoxviruses by Electron Microscopy: Optional or a Must?,” Viruses 10, no. 4 (2018): 142.

[55]

Y. Hong, B. Huang, J. Zhang, et al., “Molecular Architecture of Monkeypox Mature Virus,” Cell Discovery 10, no. 1 (2024): 108.

[56]

Y. Huang, L. Mu, and W. Wang, “Monkeypox: Epidemiology, Pathogenesis, Treatment and Prevention,” Signal Transduction and Targeted Therapy 7, no. 1 (2022): 373.

[57]

R. M. Buller and G. J. Palumbo, “Poxvirus Pathogenesis,” Microbiological Reviews 55, no. 1 (1991): 80–122.

[58]

T. Lu, Z. Wu, S. Jiang, L. Lu, and H. Liu, “The Current Emergence of Monkeypox: The Recurrence of Another Smallpox?,” Biosafety and Health 4, no. 6 (2022): 369–375.

[59]

M. R. Odom, R. C. Hendrickson, and E. J. Lefkowitz, “Poxvirus Protein Evolution: Family Wide Assessment of Possible Horizontal Gene Transfer Events,” Virus Research 144, no. 1–2 (2009): 233–249.

[60]

E. Alakunle, U. Moens, G. Nchinda, and M. I. Okeke, “Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution,” Viruses 12, no. 11 (2020): 1257.

[61]

S. Kumar, D. Guruparan, K. Karuppanan, and K. J. S. Kumar, “Comprehensive Insights Into Monkeypox (Mpox): Recent Advances in Epidemiology, Diagnostic Approaches and Therapeutic Strategies,” Pathogens 14, no. 1 (2024): 1.

[62]

W. Stern and S. Dales, “Biogenesis of Vaccinia: Concerning the Origin of the Envelope Phospholipids,” Virology 62, no. 2 (1974): 293–306.

[63]

H. A. Blough and J. M. Tiffany, “Lipids in Viruses,” Advances in Lipid Research 11 (1973): 267–339.

[64]

E. A. Boulter, “Protection Against Poxviruses,” Proceedings of the Royal Society of Medicine 62, no. 3 (1969): 295–297.

[65]

L. G. Payne, “Significance of Extracellular Enveloped Virus in the In Vitro and In Vivo Dissemination of Vaccinia,” Journal of General Virology 50, no. 1 (1980): 89–100.

[66]

L. G. Payne and K. Kristensson, “Extracellular Release of Enveloped Vaccinia Virus From Mouse Nasal Epithelial Cells In Vivo,” Journal of General Virology 66 (1985): 643–646.

[67]

B. Thornton, “The Antigenicity and Immunogenicity of the Intracellular and Extracellular Forms of Vaccinia Virus. I: The Production of High-Titre Vaccinia Extracellular Virus and Its Antigenicity After Inactivation,” British Journal of Experimental Pathology 61, no. 4 (1980):444–450.

[68]

F. M. Lum, A. Torres-Ruesta, M. Z. Tay, et al., “Monkeypox: Disease Epidemiology, Host Immunity and Clinical Interventions,” Nature Reviews Immunology 22, no. 10 (2022): 597–613.

[69]

S. N. Shchelkunov, A. V. Totmenin, P. F. Safronov, et al., “Analysis of the Monkeypox Virus Genome,” Virology 297, no. 2 (2002): 172–194.

[70]

J. Shen-Gunther, H. Cai, and Y. Wang, “Genomic and Antigenic Differences Between Monkeypox Virus and Vaccinia Vaccines: Insights and Implications for Vaccinology,” International Journal of Molecular Sciences 26, no. 4 (2025): 1428.

[71]

R. F. Massung, L. I. Liu, J. Qi, et al., “Analysis of the Complete Genome of Smallpox Variola Major Virus Strain Bangladesh—1975,” Virology 201, no. 2 (1994): 215–240.

[72]

S. N. Shchelkunov, A. V. Totmenin, V. N. Loparev, et al., “Alastrim Smallpox Variola Minor Virus Genome DNA Sequences,” Virology 266, no. 2 (2000): 361–386.

[73]

E. Alakunle, D. Kolawole, D. Diaz-Cánova, et al., “A Comprehensive Review of Monkeypox Virus and Mpox Characteristics,” Frontiers in Cellular and Infection Microbiology 14 (2024): 1360586.

[74]

C. K. Lim, J. Roberts, M. Moso, et al., “Mpox Diagnostics: Review of Current and Emerging Technologies,” Journal of Medical Virology 95, no. 1 (2023): e28429.

[75]

D. J. Esteban and A. P. Hutchinson, “Genes in the Terminal Regions of Orthopoxvirus Genomes Experience Adaptive Molecular Evolution,” BMC Genomics 12 (2011): 261.

[76]

J. Lu, H. Xing, C. Wang, et al., “Mpox (Formerly Monkeypox): Pathogenesis, Prevention, and Treatment,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 458.

[77]

E. Assarsson, J. A. Greenbaum, M. Sundström, et al., “Kinetic Analysis of a Complete Poxvirus Transcriptome Reveals an Immediate-Early Class of Genes,” PNAS 105, no. 6 (2008): 2140–2145.

[78]

J. B. Miranda, I. A. Borges, S. P. S. Campos, et al., “Serologic and Molecular Evidence of Vaccinia Virus Circulation Among Small Mammals From Different Biomes, Brazil,” Emerging Infectious Diseases 23, no. 6 (2017): 931–938.

[79]

N. P. Manes, R. D. Estep, H. M. Mottaz, et al., “Comparative Proteomics of human Monkeypox and Vaccinia Intracellular Mature and Extracellular Enveloped Virions,” Journal of Proteome Research 7, no. 3 (2008):960–968.

[80]

O. Mitjà, D. Ogoina, B. K. Titanji, et al., “Monkeypox,” Lancet 401, no. 10370 (2023): 60–74.

[81]

J. K. Locker, A. Kuehn, S. Schleich, et al., “Entry of the Two Infectious Forms of vaccinia Virus at the Plasma Membane Is Signaling-Dependent for the IMV but Not the EEV,” Molecular Biology of the Cell 11, no. 7 (2000):2497–2511.

[82]

B. Moss, “Membrane Fusion During Poxvirus Entry,” Seminars in Cell & Developmental Biology 60 (2016): 89–96.

[83]

A. Vanderplasschen, M. Hollinshead, and G. L. Smith, “Intracellular and Extracellular Vaccinia Virions Enter Cells by Different Mechanisms,” Journal of General Virology 79 (1998): 877–887.

[84]

Y. Zhang, T. Ma, T. Yuan, L. Su, D. Yu, and L. Zhong, “Recent Advances and Perspectives in Therapeutics for Mpox,” Bioorganic & Medicinal Chemistry Letters 128 (2025): 130330.

[85]

T. G. Senkevich, S. Ojeda, A. Townsley, G. E. Nelson, and B. Moss, “Poxvirus Multiprotein Entry-Fusion Complex,” PNAS 102, no. 51 (2005):18572–18577.

[86]

R. Das, A. Bhattarai, R. Karn, and B. Tamang, “Computational Investigations of Potential Inhibitors of Monkeypox Virus Envelope Protein E8 Through Molecular Docking and Molecular Dynamics Simulations,” Scientific Reports 14, no. 1 (2024): 19585.

[87]

D. Shi, P. He, Y. Song, et al., “Kinetic and Structural Aspects of Glycosaminoglycan-Monkeypox Virus Protein A29 Interactions Using Surface Plasmon Resonance,” Molecules 27, no. 18 (2022): 5898.

[88]

J. C. Hsiao, C. S. Chung, and W. Chang, “Vaccinia Virus Envelope D8L Protein Binds to Cell Surface Chondroitin Sulfate and Mediates the Adsorption of Intracellular Mature Virions to Cells,” Journal of Virology 73, no. 10 (1999): 8750–8761.

[89]

L. J. Hughes, J. Goldstein, J. Pohl, et al., “A Highly Specific Monoclonal Antibody Against Monkeypox Virus Detects the Heparin Binding Domain of A27,” Virology 464–465 (2014): 264–273.

[90]

B. Zheng, M. Duan, Y. Huang, et al., “Discovery of a Heparan Sulfate Binding Domain in Monkeypox Virus H3 as an Anti-Poxviral Drug Target Combining AI and MD Simulations,” eLife 13 (2025): RP100545.

[91]

B. Moss, “Poxvirus Cell Entry: How Many Proteins Does It Take?,” Viruses 4, no. 5 (2012): 688–707.

[92]

Q. Gong, C. Wang, X. Chuai, and S. Chiu, “Monkeypox Virus: A Re-Emergent Threat to Humans,” Virologica Sinica 37, no. 4 (2022): 477–482.

[93]

A. M. Schin, U. S. Diesterbeck, and B. Moss, “Insights Into the Organization of the Poxvirus Multicomponent Entry-Fusion Complex From Proximity Analyses in Living Infected Cells,” Journal of Virology 95, no. 16 (2021): e0085221.

[94]

T. R. Wagenaar, S. Ojeda, and B. Moss, “Vaccinia Virus A56/K2 Fusion Regulatory Protein Interacts With the A16 and G9 Subunits of the Entry Fusion Complex,” Journal of Virology 82, no. 11 (2008): 5153–5160.

[95]

C. L. Wolfe and B. Moss, “Interaction Between the G3 and L5 Proteins of the Vaccinia Virus Entry-Fusion Complex,” Virology 412, no. 2 (2011):278–283.

[96]

S. J. Chang, A. C. Shih, Y. L. Tang, and W. Chang, “Vaccinia Mature Virus Fusion Regulator A26 Protein Binds to A16 and G9 Proteins of the Viral Entry Fusion Complex and Dissociates From Mature Virions at Low pH,” Journal of Virology 86, no. 7 (2012): 3809–3818.

[97]

E. Brown, T. G. Senkevich, and B. Moss, “Vaccinia Virus F9 Virion Membrane Protein Is Required for Entry but Not Virus Assembly, in Contrast to the Related L1 Protein,” Journal of Virology 80, no. 19 (2006):9455–9464.

[98]

M. Mallardo, S. Schleich, and J. K. Locker, “Microtubule-Dependent Organization of Vaccinia Virus Core-Derived Early mRNAs Into Distinct Cytoplasmic Structures,” Molecular Biology of the Cell 12, no. 12 (2001):3875–3891.

[99]

Z. Yang, D. P. Bruno, C. A. Martens, S. F. Porcella, and B. Moss, “Simultaneous High-Resolution Analysis of vaccinia Virus and Host Cell Transcriptomes by Deep RNA Sequencing,” PNAS 107, no. 25 (2010):11513–11518.

[100]

B. Moss, “Poxvirus DNA Replication,” Cold Spring Harbor Perspectives in Biology 5, no. 9 (2013): a010199.

[101]

Z. Yang, S. E. Reynolds, C. A. Martens, D. P. Bruno, S. F. Porcella, and B. Moss, “Expression Profiling of the Intermediate and Late Stages of Poxvirus Replication,” Journal of Virology 85, no. 19 (2011): 9899–9908.

[102]

G. Sivan, A. S. Weisberg, J. L. Americo, and B. Moss, “Retrograde Transport From Early Endosomes to the Trans-Golgi Network Enables Membrane Wrapping and Egress of Vaccinia Virus Virions,” Journal of Virology 90, no. 19 (2016): 8891–8905.

[103]

D. Alzhanova and D. E. Hruby, “A Trans-Golgi Network Resident Protein, Golgin-97, Accumulates in Viral Factories and Incorporates Into Virions During Poxvirus Infection,” Journal of Virology 80, no. 23 (2006):11520–11527.

[104]

B. Sodeik, R. W. Doms, M. Ericsson, et al., “Assembly of Vaccinia Virus: Role of the Intermediate Compartment Between the Endoplasmic Reticulum and the Golgi Stacks,” Journal of Cell Biology 121, no. 3 (1993):521–541.

[105]

R. Blasco and B. Moss, “Role of Cell-Associated Enveloped Vaccinia Virus in Cell-to-Cell Spread,” Journal of Virology 66, no. 7 (1992): 4170–4179.

[106]

G. L. Smith and M. Law, “The Exit of Vaccinia Virus From Infected Cells,” Virus Research 106, no. 2 (2004): 189–197.

[107]

Y. Arakawa, J. V. Cordeiro, S. Schleich, T. P. Newsome, and M. Way, “The Release of Vaccinia Virus From Infected Cells Requires RhoA-mDia Modulation of Cortical Actin,” Cell Host & Microbe 1, no. 3 (2007): 227–240.

[108]

S. Madihi and A. Benani, “A Comprehensive Review of Current Diagnostic Techniques for Monkeypox Virus Detection,” Biologicals 91 (2025): 101841.

[109]

E. Kinganda-Lusamaki, L. K. Baketana, E. Ndomba-Mukanya, et al., “Use of Mpox Multiplex Serology in the Identification of Cases and Outbreak Investigations in the Democratic Republic of the Congo (DRC),” Pathogens 12, no. 7 (2023): 916.

[110]

L. Jiang, A. Xu, L. Guan, et al., “A Review of Mpox: Biological Characteristics, Epidemiology, Clinical Features, Diagnosis, Treatment, and Prevention Strategies,” Exploration 5, no. 2 (2025): 20230112.

[111]

Y. Zhou and Z. Chen, “Mpox: A Review of Laboratory Detection Techniques,” Archives of Virology 168, no. 8 (2023): 221.

[112]

D. Yigci, Ö. Ergönül, and S. Tasoglu, “Mpox Diagnosis at POC,” Trends in Biotechnology 43, no. 10 (2025): 2427–2439.

[113]

J. Yang, R. Guo, H. Li, et al., “Development of Highly Accurate Digital PCR Method and Reference Material for Monkeypox Virus Detection,” Analytical and Bioanalytical Chemistry 415, no. 7 (2023): 1333–1337.

[114]

E. Specchiarello, F. Carletti, G. Matusali, et al., “Development and Validation of a Nanoplate-Based Digital PCR Assay for Absolute MPXV Quantification,” Journal of Virological Methods 321 (2023): 114802.

[115]

X. Huang, F. Xiao, N. Jia, et al., “Loop-Mediated Isothermal Amplification Combined With Lateral Flow Biosensor for Rapid and Sensitive Detection of Monkeypox Virus,” Frontiers in Public Health 11 (2023):1132896.

[116]

M. Aslan, E. Seymour, H. Brickner, et al., “A Label-free Optical Biosensor-Based Point-of-Care Test for the Rapid Detection of Monkeypox Virus,” Biosensors & Bioelectronics 269 (2025): 116932.

[117]

J. Feng, G. Xue, X. Cui, et al., “Development of a Loop-Mediated Isothermal Amplification Method for Rapid and Visual Detection of Monkeypox Virus,” Microbiology Spectrum 10, no. 5 (2022): e0271422.

[118]

S. D. Davi, J. Kissenkötter, M. Faye, et al., “Recombinase Polymerase Amplification Assay for Rapid Detection of Monkeypox Virus,” Diagnostic Microbiology and Infectious Disease 95, no. 1 (2019): 41–45.

[119]

J. Farlow, M. A. Ichou, J. Huggins, and S. Ibrahim, “Comparative Whole Genome Sequence Analysis of Wild-Type and Cidofovir-resistant Monkeypoxvirus,” Virology Journal 7 (2010): 110.

[120]

S. Silva, A. Kohl, L. Pena, and K. Pardee, “Clinical and Laboratory Diagnosis of Monkeypox (Mpox): Current Status and Future Directions,” iScience 26, no. 6 (2023): 106759.

[121]

Y. Sui, Q. Xu, M. Liu, K. Zuo, X. Liu, and J. Liu, “CRISPR-Cas12a-Based Detection of Monkeypox Virus,” Journal of Infection 85, no. 6 (2022):702–769.

[122]

F. Zhao, Y. Hu, Z. Fan, et al., “Rapid and Sensitive One-Tube Detection of Mpox Virus Using RPA-Coupled CRISPR-Cas12 Assay,” Cell Reports Methods 3, no. 10 (2023): 100620.

[123]

M. Grossegesse, D. Stern, N. Hofmann, et al., “Serological Methods for the Detection of Antibodies Against Monkeypox Virus Applicable for Laboratories With Different Biosafety Levels,” Journal of Medical Virology 95, no. 12 (2023): e29261.

[124]

A. M. McCollum and I. K. Damon, “Human Monkeypox,” Clinical Infectious Diseases 58, no. 2 (2014): 260–267.

[125]

A. Tiwari, S. Adhikari, D. Kaya, et al., “Monkeypox Outbreak: Wastewater and Environmental Surveillance Perspective,” Science of the Total Environment 856 (2023): 159166.

[126]

WHO, “Mpox,” 2024, https://www.who.int/news-room/questions-and-answers/item/testing-for-mpox–health-workers.

[127]

FIND, “FIND Maintains a Searchable Directory of Diagnostic Tests for Various Diseases Under the DxConnect Umbrella,” 2025, https://finddx.shinyapps.io/testdirexplorer_beta/?inputs&sidebar=true&menubar=%22Explorer%22&button_outbreak=1.

[128]

DAAN GENE, “The Mpox Reagent (RT-qPCR),” 2024, https://daangene.com/pt/index149.html.

[129]

NMPA, “The Mpox Reagent (RT-qPCR),” 2025, https://www.cmde.org.cn/directory/web/cmde/images/1726628076135071054.pdf.

[130]

BioGerm, “The Mpox Reagent (RT-qPCR),” 2024, http://www.ivd-news.com/article/content/pid/4/id/813.html.

[131]

Sansure, “The Mpox Reagent (RT-qPCR),” 2024, https://www.sansure.com.cn/gsyw/info.aspx?itemid=2182.

[132]

B. Cabanillas, G. Murdaca, A. Guemari, et al., “Monkeypox 2024 Outbreak: Fifty Essential Questions and Answers,” Allergy 79, no. 12 (2024): 3285–3309.

[133]

F. Branda, C. Romano, M. Ciccozzi, et al., “Mpox: An Overview of Pathogenesis, Diagnosis, and Public Health Implications,” Journal of Clinical Medicine 13, no. 8 (2024): 2234.

[134]

J. S. Gootenberg, O. O. Abudayyeh, M. J. Kellner, J. Joung, J. J. Collins, and F. Zhang, “Multiplexed and Portable Nucleic Acid Detection Platform With Cas13, Cas12a, and Csm6,” Science 360, no. 6387 (2018): 439–444.

[135]

J. P. Broughton, X. Deng, G. Yu, et al., “CRISPR-Cas12-Based Detection of SARS-CoV-2,” Nature Biotechnology 38, no. 7 (2020): 870–874.

[136]

G. Hu, Z. Wei, J. Guo, et al., “A Single-Tube Two-Step MIRA-CRISPR/Cas12b Assay for the Rapid Detection of Mpox Virus,” Viruses 17, no. 6 (2025): 841.

[137]

Q. Zhang, Y. Yu, B. Yin, et al., “An Ultrasensitive and Specific CRISPR-Cas13a-Mediated Point-of-Care Assay for Monkeypox Detection and PCR-Based Clade Detection,” Infectious Diseases of Poverty 14, no. 1 (2025): 56.

[138]

J. Guo, Y. Shan, G. Hu, et al., “Rapid Visual Detection of Monkeypox Virus by One-Step LAMP-CRISPR/Cas12b Assay,” Virology Journal 22, no. 1 (2025): 151.

[139]

D. Li, K. Wilkins, A. M. McCollum, et al., “Evaluation of the GeneXpert for Human Monkeypox Diagnosis,” American Journal of Tropical Medicine and Hygiene 96, no. 2 (2017): 405–410.

[140]

M. L. Cavuto, K. Malpartida-Cardenas, I. Pennisi, et al., “Portable Molecular Diagnostic Platform for Rapid Point-of-Care Detection of Mpox and Other Diseases,” Nature Communications 16, no. 1 (2025): 2875.

[141]

WHO, “Diagnostic Testing for the Monkeypox Virus (MPXV),” 2024, https://iris.who.int/bitstream/handle/10665/376952/WHO-MPX-Laboratory-2024.1-eng.pdf?sequence=1&isAllowed=y%20(2024).

[142]

E. Ishara-Nshombo, A. Somasundaran, A. Romero-Ramirez, et al., “Diagnostic Accuracy of 3 Mpox Lateral Flow Assays for Antigen Detection, Democratic Republic of the Congo and United Kingdom,” Emerging Infectious Diseases 31, no. 6 (2025): 1140–1148.

[143]

C. Y. Liang, T. L. Chao, C. S. Chao, et al., “Monkeypox Virus A29L Protein as the Target for Specific Diagnosis and Serological Analysis,” Applied Microbiology and Biotechnology 108, no. 1 (2024): 522.

[144]

L. Ye, X. Lei, X. Xu, L. Xu, H. Kuang, and C. Xu, “Gold-Based Paper for Antigen Detection of Monkeypox Virus,” Analyst 148, no. 5 (2023): 985–994.

[145]

N. Kurosawa, T. Ozawa, K. Ozawa, et al., “Development and Clinical Evaluation of a MPXV Antigen-Detecting Rapid Diagnostic Test,” Journal of Virological Methods 337 (2025): 115164.

[146]

V. Mazzotta, S. Nozza, S. Lanini, et al., “Clinical and Laboratory Predictors of Mpox Severity and Duration: An Italian Multicentre Cohort Study (Mpox-Icona),” eBioMedicine 107 (2024): 105289.

[147]

M. A. Islam, R. Kumar, P. Sharma, S. Zhang, P. Bhattacharya, and A. Tiwari, “Wastewater‑Based Surveillance of Mpox (Monkeypox): An Early Surveillance Tool for Detecting Hotspots,” Current Pollution Reports 10 (2024): 312–325, https://doi.org/10.1007/s40726-024-00299-6.

[148]

I. Gul, C. Liu, X. Yuan, et al., “Current and Perspective Sensing Methods for Monkeypox Virus,” Bioengineering 9, no. 10 (2022): 571.

[149]

WHO, “Smallpox Vaccines,” 2016, https://www.who.int/news-room/feature-stories/detail/smallpox-vaccines.

[150]

EMA, “Summary of Product (IMVANEX) Characteristics,” 2022, https://ec.europa.eu/health/documents/community-register/2022/20220722156674/anx_156674_en.pdf.

[151]

IMVAMUNE, Product Monograph Including Patient Medication Information (IMVAMUNE, 2025), https://pdf.hres.ca/dpd_pm/00078477.PDF.

[152]

FDA, “JYNNEOS,” 2025, https://www.fda.gov/vaccines-blood-biologics/jynneos.

[153]

FDA, “ACAM2000,” 2024, https://www.fda.gov/media/75792/download?attachment.

[154]

PMDA, “LC16m8,” 2022, https://www.pmda.go.jp/PmdaSearch/iyakuDetail/GeneralList/631340K.

[155]

“Approves of Mpox Vaccine (OrthopoxVac),” State Register of Medicinal Products, 2023, https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=da624460-36a0-47be-bf46-850be407fc42.

[156]

WHO, “WHO Prequalzifies the First Vaccine Against Mpox,” 2024, https://www.who.int/news/item/13-09-2024-who-prequalifies-the-first-vaccine-against-mpox.

[157]

A. Volz and G. Sutter, “Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development,” Advances in Virus Research 97 (2017): 187–243.

[158]

A. Herrlich and A. Mayr, “Comparative Experimental Works on Cow Pox Virus Vaccines,” [in German], Archiv Fur Hygiene Und Bakteriologie 138, no. 7 (1954): 479–504.

[159]

H. Stickl and V. Hochstein-Mintzel, “[Intracutaneous Smallpox Vaccination With a Weak Pathogenic Vaccinia Virus (”MVA Virus“)],” [in German], Munchener Medizinische Wochenschrift 113, no. 35 (1971):1149–1153.

[160]

J. Reina and C. Iglesias, “Vaccines Against Monkeypox,” Medicina Clínica 160, no. 7 (2023): 305–309.

[161]

A. Volkmann, A. L. Williamson, H. Weidenthaler, et al., “The Brighton Collaboration Standardized Template for Collection of Key Information for Risk/Benefit Assessment of a Modified Vaccinia Ankara (MVA) Vaccine Platform,” Vaccine 39, no. 22 (2021): 3067–3080.

[162]

J. S. Kennedy and R. N. Greenberg, “IMVAMUNE: Modified Vaccinia Ankara Strain as an Attenuated Smallpox Vaccine,” Expert Review of Vaccines 8, no. 1 (2009): 13–24.

[163]

M. Suter, C. Meisinger-Henschel, M. Tzatzaris, et al., “Modified Vaccinia Ankara Strains With Identical Coding Sequences Actually Represent Complex Mixtures of Viruses That Determine the Biological Properties of each Strain,” Vaccine 27, no. 52 (2009): 7442–7450.

[164]

K. J. Stittelaar, T. Kuiken, R. L. de Swart, et al., “Safety of Modified Vaccinia Virus Ankara (MVA) in Immune-Suppressed Macaques,” Vaccine 19, no. 27 (2001): 3700–3709.

[165]

P. R. Pittman, M. Hahn, H. S. Lee, et al., “Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine Against Smallpox,” New England Journal of Medicine 381, no. 20 (2019): 1897–1908.

[166]

R. N. Greenberg, M. Y. Hurley, D. V. Dinh, et al., “A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18–40 Year Old Subjects With Diagnosed Atopic Dermatitis,” PLoS ONE 10, no. 10 (2015): e0138348.

[167]

E. T. Overton, J. Stapleton, I. Frank, et al., “Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial,” Open Forum Infectious Diseases 2, no. 2 (2015): ofv040.

[168]

C. M. Healy, C. B. Creech, S. E. Frey, A. Lerner, K. Tomashek, and J. H. Beigel, “579. Safety and Immunogenicity of Mpox Vaccination in Adolescents,” Open Forum Infectious Diseases 12, supplement, no. S1 (2025): ofae631017.

[169]

L. M. K. Mason, E. Betancur, M. Riera-Montes, F. Lienert, and S. Scheele, “MVA-BN Vaccine Effectiveness: A Systematic Review of Real-World Evidence in Outbreak Settings,” Vaccine 42, no. 26 (2024):126409.

[170]

L. Pischel, B. A. Martini, N. Yu, et al., “Vaccine Effectiveness of 3rd Generation Mpox Vaccines Against mpox and Disease Severity: A Systematic Review and Meta-Analysis,” Vaccine 42, no. 25 (2024): 126053.

[171]

J. D. Grabenstein and A. Hacker, “Vaccines Against Mpox: MVA-BN and LC16m8,” Expert Review of Vaccines 23, no. 1 (2024): 796–811.

[172]

CDC, “Adult Immunization Schedule by Age (Addendum updated August 7, 2025),” 2025, https://www.cdc.gov/vaccines/hcp/imz-schedules/adult-age.html?CDC_AAref_Val=https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html.

[173]

J. D. Osborne, M. Da Silva, A. M. Frace, et al., “Genomic Differences of Vaccinia Virus Clones From Dryvax Smallpox Vaccine: The Dryvax-Like ACAM2000 and the Mouse Neurovirulent Clone-3,” Vaccine 25, no. 52 (2007): 8807–8832.

[174]

J. W. LeDuc and J. Becher, “Current Status of Smallpox Vaccine,” Emerging Infectious Diseases 5, no. 4 (1999): 593–594.

[175]

M. K. Arness, R. E. Eckart, S. S. Love, et al., “Myopericarditis Following Smallpox Vaccination,” American Journal of Epidemiology 160, no. 7 (2004): 642–651.

[176]

J. M. Lane and J. D. Millar, “Risks of Smallpox Vaccination Complications in the United States,” American Journal of Epidemiology 93, no. 4 (1971): 238–240.

[177]

J. Reina and C. Iglesias, “Vaccines Against Monkeypox,” [in Spanish], Medicina Clinica 160, no. 7 (2023): 305–309.

[178]

T. P. Monath, J. R. Caldwell, W. Mundt, et al., “ACAM2000 Clonal Vero Cell Culture Vaccinia Virus (New York City Board of Health Strain)—A Second-Generation Smallpox Vaccine for Biological Defense,” International Journal of Infectious Diseases 8, supplement, no. S2 (2004): S31–S44.

[179]

R. N. Greenberg and J. S. Kennedy, “ACAM2000: A Newly Licensed Cell Culture-Based Live Vaccinia Smallpox Vaccine,” Expert Opinion on Investigational Drugs 17, no. 4 (2008): 555–564.

[180]

K. A. Marriott, C. V. Parkinson, S. I. Morefield, R. Davenport, R. Nichols, and T. P. Monath, “Clonal Vaccinia Virus Grown in Cell Culture Fully Protects Monkeys From Lethal Monkeypox Challenge,” Vaccine 26, no. 4 (2008): 581–588.

[181]

FDA, “ACAM2000,” 2025, https://www.fda.gov/vaccines-blood-biologics/vaccines/acam2000.

[182]

A. W. Artenstein, C. Johnson, T. C. Marbury, et al., “A Novel, Cell Culture-Derived Smallpox Vaccine in Vaccinia-Naive Adults,” Vaccine 23, no. 25 (2005): 3301–3309.

[183]

L. Handley, R. M. Buller, S. E. Frey, C. Bellone, and S. Parker, “The New ACAM2000 Vaccine and Other Therapies to Control Orthopoxvirus Outbreaks and Bioterror Attacks,” Expert Review of Vaccines 8, no. 7 (2009): 841–850.

[184]

B. W. Petersen, T. J. Harms, M. G. Reynolds, and L. H. Harrison, “Use of Vaccinia Virus Smallpox Vaccine in Laboratory and Health Care Personnel at Risk for Occupational Exposure to Orthopoxviruses—Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015,” Mmwr Morbidity and Mortality Weekly Report 65, no. 10 (2016): 257–262.

[185]

FDA, “Approval Letter of ACAM2000,” 2024, https://www.fda.gov/media/181430/download?attachment.

[186]

WHO, “LC16m8 (Live-Attenuated Freeze-Dried Vaccinia) Smallpox and Mpox Vaccine,” 2025, https://iris.who.int/bitstream/handle/10665/381313/B09388-eng.pdf?sequence=1.

[187]

WHO, “Recommendation For An Emergency Use Listing of “Freeze-Dried Smallpox Vaccine Prepared In Cell Culture Lc16” ‘Kmb’ (Lc16m8 Vaccine) Submitted By Km Biologics, Japan,” 2024, https://extranet.who.int/prequal/sites/default/files/document_files/mpox-lc16m8_tag-report-19-11-2024-final.pdf.

[188]

M. Sugimoto, A. Yasuda, K. Miki, et al., “Gene Structures of Low-Neurovirulent Vaccinia Virus LC16m0, LC16m8, and Their Lister Original (LO) Strains,” Microbiology and Immunology 29, no. 5 (1985): 421–428.

[189]

S. Morikawa, T. Sakiyama, H. Hasegawa, et al., “An Attenuated LC16m8 Smallpox Vaccine: Analysis of Full-Genome Sequence and Induction of Immune Protection,” Journal of Virology 79, no. 18 (2005):11873–11891.

[190]

M. Saijo, Y. Ami, Y. Suzaki, et al., “LC16m8, a Highly Attenuated Vaccinia Virus Vaccine Lacking Expression of the Membrane Protein B5R, Protects Monkeys From Monkeypox,” Journal of Virology 80, no. 11 (2006):5179–5188.

[191]

C. A. Meseda, A. E. Mayer, A. Kumar, et al., “Comparative Evaluation of the Immune Responses and Protection Engendered by LC16m8 and Dryvax Smallpox Vaccines in a Mouse Model,” Clinical and Vaccine Immunology 16, no. 9 (2009): 1261–1271.

[192]

I. Iizuka, Y. Ami, Y. Suzaki, et al., “A Single Vaccination of Nonhuman Primates With Highly Attenuated Smallpox Vaccine, LC16m8, Provides Long-term Protection Against Monkeypox,” Japanese Journal of Infectious Diseases 70, no. 4 (2017): 408–415.

[193]

K. Kobiyama, D. Utsumi, Y. Kaku, et al., “Immunological Analysis of LC16m8 Vaccine: Preclinical and Early Clinical Insights Into mpox,” eBioMedicine 115 (2025): 105703.

[194]

J. S. Kennedy, M. Gurwith, C. L. Dekker, et al., “Safety and Immunogenicity of LC16m8, an Attenuated Smallpox Vaccine in Vaccinia-Naive Adults,” Journal of Infectious Diseases 204, no. 9 (2011): 1395–1402.

[195]

E. Morino, S. Mine, N. Tomita, et al., “Mpox Neutralizing Antibody Response to LC16m8 Vaccine in Healthy Adults,” NEJM Evidence 3, no. 3 (2024): EVIDoa2300290.

[196]

N. Okumura, E. Morino, H. Nomoto, et al., “LC16m8 for Pre-Exposure Prophylaxis Against Mpox in a High-Risk Population: An Open-Label Randomized Trial,” Clinical Infectious Diseases (2025): ciaf074.

[197]

R. Yano, J. Terada-Hirashima, Y. Uemura, et al., “Efficacy and Safety of the Smallpox Vaccine for Postexposure Prophylaxis in Monkeypox: Protocol for an Open-Labeled, Single-Armed Study,” JMIR Research Protocols 12 (2023): e46955.

[198]

N. Tomita, J. Terada-Hirashima, Y. Uemura, et al., “An Open-Label, Non-Randomized Study Investigating the Safety and Efficacy of Smallpox Vaccine, LC16, as Post-Exposure Prophylaxis for mpox,” Human Vaccines & Immunotherapeutics 19, no. 2 (2023): 2242219.

[199]

WHO, “WHO Adds LC16m8 Mpox Vaccine to Emergency Use Listing,” 2024, https://www.who.int/news/item/19-11-2024-who-adds-lc16m8-mpox-vaccine-to-emergency-use-listing.

[200]

“Efficacy/Effectiveness, Safety, and Immunogenicity of LC16m8 Mpox Vaccine in Colombia (MPOX-COL),” Clinicaltrials, 2025, https://clinicaltrials.gov/study/NCT06223919.

[201]

N. Tomotsugu, M. J. Amaya-Mahecha, M. Hamana, et al., “Key Success Factors in Clinical Trial Operation of the Smallpox Vaccine LC16m8 Against Mpox in Colombia,” Global Health & Medicine 7, no. 2 (2025): 180–184.

[202]

R. A. Maksyutov, S. N. Yakubitskiy, I. V. Kolosova, et al., “Genome Stability of the Vaccine Strain VACΔ6,” Vavilovskii Zhurnal Genetiki i Selektsii 26, no. 4 (2022): 394–401.

[203]

R. A. Maksyutov, S. N. Yakubitskyi, I. V. Kolosova, and S. N. Shchelkunov, “Comparing New-Generation Candidate Vaccines Against Human Orthopoxvirus Infections,” Acta Naturae 9, no. 2 (2017): 88–93.

[204]

“Russia Plans to Start Production of Smallpox Vaccine,” Federal Service for Surveillance in Healthcare, 2023, https://roszdravnadzor.gov.ru/spec/news/36364.

[205]

A. Zuiani, C. L. Dulberger, N. S. De Silva, et al., “A Multivalent mRNA Monkeypox Virus Vaccine (BNT166) Protects Mice and Macaques From Orthopoxvirus Disease,” Cell 187, no. 6 (2024): 1363–1373.e12.

[206]

E. M. Mucker, A. W. Freyn, S. L. Bixler, et al., “Comparison of Protection Against Mpox Following mRNA or Modified Vaccinia Ankara Vaccination in Nonhuman Primates,” Cell 187, no. 20 (2024):5540–5553.e10.

[207]

Y. Q. Zhai, Y. Z. Han, W. L. Wang, and W. J. Tan, “Advancements in Mpox Vaccine Development: A Comprehensive Review of Global Progress and Recent Data,” Biomedical and Environmental Sciences 38, no. 2 (2025):248–254.

[208]

Q. Chu, B. Huang, M. Li, et al., “Non-Replicating Vaccinia Virus NTV as an Effective Next-Generation Smallpox and Monkeypox Vaccine: Evidence From Mouse and Rhesus Monkey Models,” Emerging Microbes & Infections 12, no. 2 (2023): 2278900.

[209]

“The Clinical Trial Application for JT118 Injection Was Accepted,” Webull, 2024, https://www.webull.com/news/12972069077885952.

[210]

CDC, “Clinical Treatment of Mpox,” 2025, https://www.cdc.gov/mpox/hcp/clinical-care/index.html.

[211]

A. Hallo-Carrasco, C. L. Hunt, C. C. Prusinski, et al., “Pain Associated with Monkeypox Virus: A Rapid Review,” Cureus 15, no. 2 (2023): e34697.

[212]

Labeling of TPOXX,” FDA, 2018, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208627Orig1s000Lbl.pdf.

[213]

C. E. DeLaurentis, J. Kiser, and J. Zucker, “New Perspectives on Antimicrobial Agents: Tecovirimat for Treatment of Human Monkeypox Virus,” Antimicrobial Agents and Chemotherapy 66, no. 12 (2022): e0122622.

[214]

R. Vernuccio, A. Martínez León, C. S. Poojari, et al., “Structural Insights Into Tecovirimat Antiviral Activity and Poxvirus Resistance,” Nature microbiology 10, no. 3 (2025): 734–748.

[215]

D. W. Grosenbach, R. Jordan, and D. E. Hruby, “Development of the Small-Molecule Antiviral ST-246 as a Smallpox Therapeutic,” Future Virology 6, no. 5 (2011): 653–671.

[216]

Labeling of Vistide,” FDA, 2000, https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/020638s003lbl.pdf.

[217]

T. G. Sobral-Costas, R. Escudero-Tornero, G. Servera-Negre, et al., “Human Monkeypox Outbreak: Epidemiological Data and Therapeutic Potential of Topical Cidofovir in a Prospective Cohort Study,” Journal of the American Academy of Dermatology 88, no. 5 (2023): 1074–1082.

[218]

Labeling of TEMBEXA,” FDA, 2021, https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214460s000,214461s000lbl.pdf.

[219]

SIGA, “Interim Results from STOMP Study of SIGA's Tecovirimat in Treatment of Mpox Announced,” 2024, https://investor.siga.com/investors/news/news-details/2024/Interim-Results-from-STOMP-Study-of-SIGAs-Tecovirimat-in-Treatment-of-Mpox-Announced/default.aspx.

[220]

R. Ali, J. Alonga, J. L. Biampata, et al., “Tecovirimat for Clade I MPXV Infection in the Democratic Republic of Congo,” New England Journal of Medicine 392, no. 15 (2025): 1484–1496.

[221]

A. T. Russo, D. W. Grosenbach, J. Chinsangaram, et al., “An Overview of Tecovirimat for Smallpox Treatment and Expanded Anti-Orthopoxvirus Applications,” Expert Review of Anti-Infective Therapy 19, no. 3 (2021): 331–344.

[222]

G. Yang, D. C. Pevear, M. H. Davies, et al., “An Orally Bioavailable Antipoxvirus Compound (ST-246) Inhibits Extracellular Virus Formation and Protects Mice From Lethal Orthopoxvirus Challenge,” Journal of Virology 79, no. 20 (2005): 13139–13149.

[223]

M. Almehmadi, M. Allahyani, A. A. Alsaiari, et al., “A Glance at the Development and Patent Literature of Tecovirimat: The First-in-Class Therapy for Emerging Monkeypox Outbreak,” Viruses 14, no. 9 (2022):1870.

[224]

U.S. Department of Health and Human Services, Center for Drug Evaluation and Research, and Center for Biologics Evaluation and Research. Product Development Under the Animal Rule Guidance for Industry. (FDA, 2015), https://www.fda.gov/media/88625/download.

[225]

FDA, “Clinical Reviews,” 2018, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208627Orig1s000MedR.pdf.

[226]

FDA, “Non-Clinical Reviews,” 2018, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208627Orig1s000PharmR.pdf.

[227]

A. Amantana, Y. Chen, S. R. Tyavanagimatt, et al., “Pharmacokinetics and Interspecies Allometric Scaling of ST-246, an Oral Antiviral Therapeutic for Treatment of Orthopoxvirus Infection,” PLoS ONE 8, no. 4 (2013): e61514.

[228]

A. Laudisoit, F. Tepage, and R. Colebunders, “Oral Tecovirimat for the Treatment of Smallpox,” New England Journal of Medicine 379, no. 21 (2018): 2084–2085.

[229]

M. Merchlinsky, A. Albright, V. Olson, et al., “The Development and Approval of Tecoviromat (TPOXX()), the First Antiviral Against Smallpox,” Antiviral Research 168 (2019): 168–174.

[230]

FDA, “Approval Letter of TPOXX Capsule,” 2018, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208627Orig1s000Approv.pdf.

[231]

FDA, “Combined Cross-Discipline Team Leader, Clinical, Clinical Pharmacology, and Division Director Review,” 2022, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/214518Orig1s000MultidisciplineR.pdf.

[232]

A. T. Russo, D. W. Grosenbach, K. M. Honeychurch, P. G. Long, and D. E. Hruby, “Overview of the Regulatory Approval of tecovirimat Intravenous Formulation for Treatment of smallpox: Potential Impact on Smallpox Outbreak Response Capabilities, and Future tecovirimat Development Potential,” Expert Review of Anti-Infective Therapy 21, no. 3 (2023): 235–242.

[233]

FDA, “Label of TPOXX Injection,” 2022, https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214518s000lbl.pdf.

[234]

TPD, “TPOXX, Product Monograph of TPOXX Capsule,” 2021, https://pdf.hres.ca/dpd_pm/00081057.PDF.

[235]

EMA, “Tecovirimat SIGA: EPAR—Medicine Overview,” 2022, https://www.ema.europa.eu/en/documents/overview/tecovirimat-siga-epar-medicine-overview_en.pdf.

[236]

MHRA, “Summary of Product Characteristics,” 2022, https://mhraproducts4853.blob.core.windows.net/docs/b572d615258c1ef0680a02292f8a22abf6fd591e.

[237]

PMDA, “TEPOXX,” 2024, https://www.pmda.go.jp/PmdaSearch/iyakuDetail/GeneralList/625005Y.

[238]

P. A. Yu, R. Elmor, K. Muhammad, Y. C. Yu, and A. K. Rao, “Tecovirimat Use Under Expanded Access to Treat Mpox in the United States, 2022–2023,” NEJM Evidence 3, no. 10 (2024): EVIDoa2400189.

[239]

A. R. Raccagni, D. Leoni, A. Ciccullo, et al., “Rapid Improvement of Severe Mpox Lesions With Oral Tecovirimat,” Journal of Medical Virology 95, no. 6 (2023): e28825.

[240]

K. O'Laughlin, F. A. Tobolowsky, R. Elmor, et al., “Clinical Use of Tecovirimat (Tpoxx) for Treatment of Monkeypox under an Investigational New Drug Protocol—United States, May–August 2022,” Mmwr Morbidity and Mortality Weekly Report 71, no. 37 (2022): 1190–1195.

[241]

M. Tempestilli, A. Mondi, A. D'Avolio, et al., “Pharmacokinetics of Tecovirimat in Subjects With Mpox,” International Journal of Antimicrobial Agents 63, no. 2 (2024): 107068.

[242]

C. Vo, R. Zomorodi, R. Silvera, et al., “Clinical Characteristics and Outcomes of Patients With Mpox Who Received Tecovirimat in a New York City Health System,” Open Forum Infectious Diseases 10, no. 11 (2023): ofad552.

[243]

E. L. Wu, R. L. Osborn, C. M. Bertram, et al., “Tecovirimat Use in Ambulatory and Hospitalized Patients with Monkeypox Virus Infection,” Sexually Transmitted Diseases 50, no. 3 (2023): 172–174.

[244]

K. K. Demir, M. Desjardins, C. Fortin, et al., “Treatment of Severe Human Mpox Virus Infection With Tecovirimat: A Case Series,” Canada Communicable Disease Report 49, no. 2–3 (2023): 76–80.

[245]

B. Aldred, R. H. Lyles, J. Y. Scott, et al., “Early Tecovirimat Treatment for Mpox Disease Among People with HIV,” JAMA Internal Medicine 184, no. 3 (2024): 275–279.

[246]

A. Mondi, R. Gagliardini, V. Mazzotta, et al., “Clinical Experience With Use of Oral Tecovirimat or Intravenous Cidofovir for the Treatment of Monkeypox in an Italian Reference Hospital,” Journal of Infection 86, no. 1 (2023): 66–117.

[247]

SIGA Technologies, “Topline Results From PALM 007 Study of SIGA's Tecovirimat in Treatment of Mpox,” 2024, https://s204.q4cdn.com/957130458/files/doc_news/2024/08/08-15-2024_SIGA_PALM-007-Press-Release_FINAL-FINAL.pdf.

[248]

J. McLean, K. Stoeckle, S. Huang, et al., “Tecovirimat Treatment of People with HIV During the 2022 Mpox Outbreak: A Retrospective Cohort Study,” Annals of Internal Medicine 176, no. 5 (2023): 642–648.

[249]

J. P. Lalezari, R. J. Stagg, B. D. Kuppermann, et al., “Intravenous Cidofovir for Peripheral Cytomegalovirus Retinitis in Patients With AIDS. A Randomized, Controlled Trial,” Annals of Internal Medicine 126, no. 4 (1997): 257–263.

[250]

N. Narsana, D. Ha, and D. Y. Ho, “Treating Adenovirus Infection in Transplant Populations: Therapeutic Options beyond Cidofovir?,” Viruses 17, no. 5 (2025): 599.

[251]

L. Sallée and D. Boutolleau, “Management of Refractory/Resistant Herpes Simplex Virus Infections in Haematopoietic Stem Cell Transplantation Recipients: A Literature Review,” Reviews in Medical Virology 34, no. 5 (2024): e2574.

[252]

J. Piret and G. Boivin, “Antiviral Drugs against Herpesviruses,” Advances in Experimental Medicine and Biology 1322 (2021): 1–30.

[253]

E. De Clercq, T. Sakuma, M. Baba, et al., “Antiviral Activity of Phosphonylmethoxyalkyl Derivatives of Purine and Pyrimidines,” Antiviral Research 8, no. 5–6 (1987): 261–272.

[254]

R. O. Baker, M. Bray, and J. W. Huggins, “Potential Antiviral Therapeutics for Smallpox, Monkeypox and Other Orthopoxvirus Infections,” Antiviral Research 57, no. 1–2 (2003): 13–23.

[255]

E. De Clercq, “Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections,” Clinical Microbiology Reviews 16, no. 4 (2003):569–596.

[256]

D. F. Smee, “Progress in the Discovery of Compounds Inhibiting Orthopoxviruses in Animal Models,” Antiviral Chemistry & Chemotherapy 19, no. 3 (2008): 115–124.

[257]

G. Andrei and R. Snoeck, “Cidofovir Activity Against Poxvirus Infections,” Viruses 2, no. 12 (2010): 2803–2830.

[258]

J. Prévost, A. Sloan, Y. Deschambault, et al., “Treatment Efficacy of Cidofovir and Brincidofovir Against Clade II Monkeypox Virus Isolates,” Antiviral Research 231 (2024): 105995.

[259]

C. Fabrizio, G. Bruno, L. Cristiano, and G. B. Buccoliero, “Cidofovir for Treating Complicated Monkeypox in a Man With Acquired Immune Deficiency Syndrome,” Infection 51, no. 2 (2023): 519–522.

[260]

A. K. Rao, C. A. Schrodt, F. S. Minhaj, et al., “Interim Clinical Treatment Considerations for Severe Manifestations of Mpox—United States, February 2023,” Mmwr Morbidity and Mortality Weekly Report 72, no. 9 (2023): 232–243.

[261]

A. K. Gupta, M. Talukder, T. Rosen, and V. Piguet, “Differential Diagnosis, Prevention, and Treatment of mpox (Monkeypox): A Review for Dermatologists,” American Journal of Clinical Dermatology 24, no. 4 (2023): 541–556.

[262]

A. A. Hershan, “Virology, Epidemiology, Transmissions, Diagnostic Tests, Prophylaxis and Treatments of human Mpox: Saudi Arabia Perspective,” Frontiers in Cellular and Infection Microbiology 15 (2025):1530900.

[263]

S. L. Ciesla, J. Trahan, W. B. Wan, et al., “Esterification of cidofovir With Alkoxyalkanols Increases Oral Bioavailability and Diminishes Drug Accumulation in Kidney,” Antiviral Research 59, no. 3 (2003): 163–171.

[264]

FDA, “Drug Approval Package: TEMBEXA,” accessed October 20, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214460Orig1s000,%20214461Orig1s000TOC.cfm.

[265]

CDC, Enrollment Starts in Africa CDC-LED Mpox Therapeutic Study (MOSA). (2025). Accessed 20 October 2025, Retrieved from, https://africacdc.org/news-item/enrollment-starts-in-africa-cdc-led-mpox-therapeutic-study-mosa/.

[266]

J. Cinatl, M. Bechtel, P. Reus, et al., “Trifluridine for Treatment of Mpox Infection in Drug Combinations in Ophthalmic Cell Models,” Journal of Medical Virology 96, no. 1 (2024): e29354.

[267]

A. Abdelaal, A. Reda, A. R. Hassan, et al., “Monkeypox-Associated Manifestations and Complications Involving the Eye: A Systematic Review and Meta-Analysis of Previous and Current Outbreaks,” Asia-Pacific journal of ophthalmology (Philadelphia) 12, no. 3 (2023): 326–337.

[268]

S. Cash-Goldwasser, S. M. Labuda, D. W. McCormick, et al., “Ocular Monkeypox—United States, July-September 2022,” Mmwr Morbidity and Mortality Weekly Report 71, no. 42 (2022): 1343–1347.

[269]

B. Perzia, D. Theotoka, K. Li, et al., “Treatment of Ocular-involving Monkeypox Virus With Topical Trifluridine and Oral Tecovirimat in the 2022 Monkeypox Virus Outbreak,” American Journal of Ophthalmology Case Reports 29 (2023): 101779.

[270]

M. A. Shamim, P. Satapathy, B. K. Padhi, et al., “Pharmacological Treatment and Vaccines in monkeypox Virus: A Narrative Review and Bibliometric Analysis,” Frontiers in pharmacology 14 (2023): 1149909.

[271]

L. N. Shishkina, O. Y. Mazurkov, N. I. Bormotov, et al., “Safety and Pharmacokinetics of the Substance of the Anti-Smallpox Drug NIOCH-14 After Oral Administration to Laboratory Animals,” Viruses 15, no. 1 (2023):205.

[272]

Shenzhen Weixin Biotechnology Co., “A Class of Acylhydrazine Compounds, Their Preparation Methods and Their Applications,” 2022. China patent CN116003309B.

[273]

V. A. Shiryaev, M. Y. Skomorohov, M. V. Leonova, et al., “Adamantane Derivatives as Potential Inhibitors of p37 Major Envelope Protein and Poxvirus Reproduction. Design, Synthesis and Antiviral Activity,” European Journal of Medicinal Chemistry 221 (2021): 113485.

[274]

D. C. Quenelle, D. J. Collins, B. P. Herrod, et al., “Effect of Oral Treatment With Hexadecyloxypropyl-[(S)-9-(3-Hydroxy-2- Phosphonylmethoxypropyl) Adenine] [(S)-HPMPA] or Octadecyloxyethyl-(S)-HPMPA on Cowpox or Vaccinia Virus Infections in Mice,” Antimicrobial Agents and Chemotherapy 51, no. 11 (2007): 3940–3947.

[275]

Y. Zhang, Y. Wan, C. Guo, et al., “Novel Derivatives of Brincidofovir and (S)-9-(3-Hydroxy-2-Phosphonylmethoxypropyl)Adenine Inhibit Orthopoxviruses and Human Adenoviruses More Potently Than Brincidofovir,” Signal Transduction and Targeted Therapy 10, no. 1 (2025):114.

[276]

J. Liu, Q. Zhao, Y. Zhai, et al., “Safety, Tolerability and Pharmacokinetics of ASC10, a Novel Oral Double Prodrug of a Broad-Spectrum Antiviral Agent, β-d-N4-Hydroxycytidine: Results From a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study in Chinese Healthy Subjects,” Expert Opinion on Investigational Drugs 33, no. 8 (2024):867–876.

[277]

Ascletis, “Ascletis Announces IND Approval of Viral Polymerase Inhibitor ASC10 for Monkeypox Indication by U.S. FDA,” 2025, https://www.ascletis.com/news_detail/179/id/762.html.

[278]

D. E. Martínez-Fernández, D. Fernández-Quezada, F. A. G. Casillas-Muñoz, et al., “Human Monkeypox: A Comprehensive Overview of Epidemiology, Pathogenesis, Diagnosis, Treatment, and Prevention Strategies,” Pathogens 12, no. 7 (2023): 947.

[279]

CIDRAP, “FDA Approves VIG for Smallpox Shot Complications,”2005, https://www.cidrap.umn.edu/smallpox/fda-approves-vig-smallpox-shot-complications.

[280]

NIH, “CNJ-016,” accessed October 20, 2025, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4f9f620-e6e4-4a03-a9a7-79007c8c2cfe.

[281]

K. G. Piparva, N. Fichadiya, T. Joshi, and S. Malek, “Monkeypox: From Emerging Trends to Therapeutic Concerns,” Cureus 16, no. 4 (2024): e58866.

[282]

CDC, “Informed Consent/Parental Permission Form for Vaccinia Immune Globulin Intravenous Treatment Under An Expanded Access Investigational New Drug (IND) Program,” 2025, https://www.cdc.gov/mpox/media/pdfs/Attachment-2_VIGIV-Informed-Consent-Form.pdf.

[283]

Y. Gao, X. Xie, X. Zhang, et al., “Substrate Recognition and Cleavage Mechanism of the Monkeypox Virus Core Protease,” Nature 643, no. 8070 (2025): 271–279.

[284]

M. Zgarbová, T. Otava, J. Silhan, R. Nencka, J. Weber, and E. Boura, “Inhibitors of Mpox VP39 2'-O Methyltransferase Efficiently Inhibit the Monkeypox Virus,” Antiviral Research 218 (2023): 105714.

[285]

K. Chiem, A. Nogales, M. Lorenzo, et al., “Identification of In Vitro Inhibitors of Monkeypox Replication,” Microbiology Spectrum 11, no. 4 (2023): e0474522.

[286]

E. N. Karmarkar, M. R. Golden, R. P. Kerani, et al., “Association of Tecovirimat Therapy with Mpox Symptom Improvement: A Cross-Sectional Study-King County, Washington, May–October 2022,” Open Forum Infectious Diseases 11, no. 3 (2024): ofae029.

[287]

E. A. Garcia, M. M. K. Foote, T. D. McPherson, et al., “Severe Mpox Among People with Advanced Human Immunodeficiency Virus Receiving Prolonged Tecovirimat in New York City,” Open Forum Infectious Diseases 11, no. 6 (2024): ofae294.

[288]

A. Karan, N. Shah, J. M. Garrigues, et al., “Surveillance of Complicated Mpox Cases Unresponsive to Oral Tecovirimat in Los Angeles County, 2022,” Journal of Infectious Diseases 229, supplement, no. S2 (2024): S249–S254.

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