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9 pages, 1330 KB  
Case Report
Genomic Characterization of the Index Case of Human Monkeypox Virus Infection in Mali, 2025
by Noumou Yakhouba Keita, Mahamadou Abdou, Mohamed Ag Baraïka, Klema Marcel Kone, Ousmane Kamena, Elysabette Coulibaly, Mariam Sama Sangare, Korika Diakite, Dorcas Waruguru Wanjohi, Boubacar Doumbia, Harris Onywera, Moussa Moise Diagne and Ibrehima Guindo
Viruses 2026, 18(3), 294; https://doi.org/10.3390/v18030294 - 28 Feb 2026
Viewed by 300
Abstract
Mpox is a zoonosis caused by the monkeypox virus. Here, we report Mali’s index Mpox case, which was clinically identified at the Mali–Guinea border by the national telemedicine center and confirmed by PCR. The library prepared with NextGenPCR™ MPXV Sequencing Library Prep and [...] Read more.
Mpox is a zoonosis caused by the monkeypox virus. Here, we report Mali’s index Mpox case, which was clinically identified at the Mali–Guinea border by the national telemedicine center and confirmed by PCR. The library prepared with NextGenPCR™ MPXV Sequencing Library Prep and sequenced on Minion MK1C revealed a genome length of 197,122 bp with an average depth of 1284.4×. The strain belonged to Clade IIb G1 lineage and exhibited 85 mutations relative to NC_063383.1. To decipher genomic epidemiology, genomes ≥ 195 kb were retrieved from NCBI and aligned with MAFFT. Time-resolved phylogenetic reconstruction and ancestral trait inference were performed with TreeTime v0.11.4. A median joining network was built with Popart v1.7. Phylogeographic analysis revealed clustering with Clade IIb (G.1 lineage) linked to the May 2025 outbreak in Sierra Leone. Full article
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9 pages, 228 KB  
Article
Beyond Foodborne HAV: Sexual Transmission Drives a New Wave of Cases in Romania
by Adrian Paun, Irina Ianache, Ruxandra Moroti, Georgiana Pomohaci, Gratiela Tardei, Mike Youle, Simona Ruta and Cristiana Oprea
Viruses 2026, 18(2), 215; https://doi.org/10.3390/v18020215 - 6 Feb 2026
Viewed by 395
Abstract
Background: In 2022, Romania experienced a sharp increase in hepatitis A virus (HAV) infections, with evidence of predominant fecal–oral transmission through sexual contact, raising concern for an outbreak among men who have sex with men (MSM). Methods: We conducted a prospective [...] Read more.
Background: In 2022, Romania experienced a sharp increase in hepatitis A virus (HAV) infections, with evidence of predominant fecal–oral transmission through sexual contact, raising concern for an outbreak among men who have sex with men (MSM). Methods: We conducted a prospective multicenter study between 1 March 2022 and 1 March 2023 in two tertiary hospitals in Bucharest. HAV infection was defined by a compatible clinical presentation, elevated liver enzymes, and positive anti-HAV IgM serology. Clinical and laboratory characteristics were compared by transmission route and HIV status. Results: A total of 191 patients were diagnosed with HAV, including 105 MSM and 86 with foodborne transmission. All were unvaccinated. Most patients were male (82.2%), with a median age of 30 years (IQR 24–38). MSM were significantly younger and reported higher-risk sexual behaviors, including chemsex and multiple or occasional partners (p < 0.0001). Among MSM, 48 (25.1%) were living with HIV, most with preserved immune status and undetectable viral loads. Clinical manifestations were similar across groups, with jaundice being most frequent (89.5%). However, MSM exhibited more severe hepatocellular injury, reflected by higher ASAT and ALAT levels and lower prothrombin concentration, independent of HIV status. MSM were also more likely to have concomitant sexually transmitted infections, including syphilis and mpox (p < 0.001). Disease was predominantly mild, although MSM had longer hospital stays. Conclusions: The 2022 HAV surge in Romania was driven by both sexual and foodborne transmission. Targeted HAV vaccination, along with integrated sexual health services and harm-reduction strategies, is essential to prevent future outbreaks. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis Co-Infection)
19 pages, 2276 KB  
Article
Insights into Genomic Dynamics and Plasticity in the Monkeypox Virus from the 2022 Outbreak
by Michela Deiana, Elena Locatelli, Laura Veschetti, Simone Malagò, Antonio Mori, Denise Lavezzari, Silvia Accordini, Niccolò Ronzoni, Andrea Angheben, Giovanni Malerba, Evelina Tacconelli, Maria Grazia Cusi, Federico Giovanni Gobbi, Chiara Piubelli and Concetta Castilletti
Int. J. Mol. Sci. 2026, 27(3), 1371; https://doi.org/10.3390/ijms27031371 - 29 Jan 2026
Viewed by 529
Abstract
The 2022 global mpox outbreak represented a turning point in the Monkeypox virus (MPXV) epidemiology, highlighting the incredible capability of this virus to adapt to different conditions, also in a non-endemic context. To investigate the genomic dynamics of MPXV 2022 strains, we performed [...] Read more.
The 2022 global mpox outbreak represented a turning point in the Monkeypox virus (MPXV) epidemiology, highlighting the incredible capability of this virus to adapt to different conditions, also in a non-endemic context. To investigate the genomic dynamics of MPXV 2022 strains, we performed whole-genome sequencing of 40 clinical samples from 16 Italian patients across multiple anatomical sites and timepoints between May and December 2022. Combining single-nucleotide analysis with detailed investigation of short tandem repeats (STRs), we explored inter- and intra-host viral dynamics. We identified 19 STR loci located near or within genes involved in immune modulation and virion morphogenesis. While most STRs remained stable across patients, a subset displayed locus- or matrix-specific variation. Among these, STR-VII—embedded within the coding sequence of OPG153, an envelope-associated protein implicated in viral attachment—showed a 12-nucleotide in-frame deletion, resulting in the loss of four aspartic acid residues (Δ4D variant). Structural modeling indicated that this deletion slightly alters a disordered acidic loop without affecting the global fold, potentially modulating surface charge and immune recognition. Integrating STR profiling into genomic surveillance may enhance resolution in outbreak reconstruction and reveal subtle adaptive processes underlying poxvirus–host interaction and immune escape. Full article
(This article belongs to the Special Issue Viral Biology: Infection and Pathology, Diagnosis and Treatment)
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34 pages, 4203 KB  
Review
Insights into Monkeypox Virus: Host Immunity, Viral Immune Evasion, Recent Advances in Vaccines, Therapeutic Development, and Future Perspectives
by Mingzhuo Chen, Weigang Ren, Xin Wu, Jamal Muhammad Khan, Humera Nazir, Shafeeq Ur Rehman, Faizan Ali and Junwei Li
Microorganisms 2026, 14(2), 317; https://doi.org/10.3390/microorganisms14020317 - 29 Jan 2026
Viewed by 966
Abstract
Monkeypox (Mpox), a zoonotic viral disease caused by the Monkeypox Virus (MPXV), has gained significant attention in recent years due to its increasing incidence and the grave threat it poses to global health. MPXV has spread at a rapid pace during the COVID-19 [...] Read more.
Monkeypox (Mpox), a zoonotic viral disease caused by the Monkeypox Virus (MPXV), has gained significant attention in recent years due to its increasing incidence and the grave threat it poses to global health. MPXV has spread at a rapid pace during the COVID-19 pandemic, causing 10,000+ confirmed cases and ~300 fatalities in 122 countries. This virus comprises two major clades, Clade I (Central African), which is evidently more virulent, and Clade II (West African), which has caused the recent outbreaks across the world and caused fewer deaths. Clinically, Mpox presents as a milder form with fever, lymphadenopathy, and vesiculopustular rash similar to smallpox. Diagnostic measures such as polymerase chain reaction (PCR) are the main diagnostic confirmatory tools. Advanced diagnostics involve electronic microscopy, serology, and immunohistochemistry. Alternative drugs like tecovirimat and brincidofovir have demonstrated potential for treating smallpox, but there is scanty evidence on their efficacy against MPXV. Most recent advancements in the study of vaccines have resulted in the creation and introduction of MVA-BN (JYNNEOS/Imvanex/Imvamune) and ACAM2000 vaccines, which conferred cross-protection against MPXV. MVA-BN is suggested to perform better than other types due to its enhanced safety and immunogenicity. Researchers are also developing DNA and protein subunit vaccines against Mpox to induce specific immune responses by presenting viral proteins. The discovery of novel vaccine candidates and antiviral treatments will be needed to prevent future outbreaks and reduce the global health burden of Mpox. This review focuses on the characterization of MPXV, summarizing current knowledge on its genomic structure, pathogenesis, replication, potential targets of anti-MPXV drugs, clinical features, and epidemiological patterns, along with recent advances in vaccine development. Full article
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16 pages, 728 KB  
Systematic Review
Clinical Features and Epidemiology of Mpox in Saudi Arabia Post-2022 Re-Emergence: A Systematic Review of Case Reports and Series
by Ethar Alsulami, Roudin H. Alhasawi, Abdulaziz F. Samandar, Omnia A. Sulimani, Safia H. Alansari, Shahad A. Alshehri, Reem A. Alshehri, Saud A. Al-luhaypi and Mazin M. Aljabri
Zoonotic Dis. 2026, 6(1), 3; https://doi.org/10.3390/zoonoticdis6010003 - 28 Jan 2026
Viewed by 356
Abstract
Background: With the worldwide resurgence of Mpox in 2022, understanding its regional features is important. This systematic review aimed to provide an overview of the epidemiology, risk factors, clinical features, and outcomes of Mpox in Saudi Arabia to fill the knowledge gaps in [...] Read more.
Background: With the worldwide resurgence of Mpox in 2022, understanding its regional features is important. This systematic review aimed to provide an overview of the epidemiology, risk factors, clinical features, and outcomes of Mpox in Saudi Arabia to fill the knowledge gaps in this area. Methods: Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic search was performed on PubMed, MEDLINE (via Ovid), Scopus and Wiley Online Library for case reports and series published on Mpox in Saudi Arabia after 2022. Results: Analysis included eight studies comprising a total of 410 patients with confirmatory data. The cohort was predominantly male (91%), with a mean age of 32.8 years. Extramarital sexual contact was the most frequently identified risk factor (28.8%), whereas most patients (63.4%) had unknown or denied exposure routes. The most common clinical manifestations were fever (97.1%) and rash (96.8%). Dermatological findings were usually pleomorphic. These included umbilicated pustules, crusted papules, and vesiculopustular lesions. Although management was primarily supportive, rare complications, such as keratitis and neurological deficits, were observed. Conclusions: In Saudi Arabia, Mpox primarily affects young adult males, particularly individuals with high-risk sexual behaviors. Much of this transmission remains undetermined, and better contact tracing and focused public health efforts are urgently required. Full article
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11 pages, 876 KB  
Article
Robust Adaptive Immunity to MPXV in Older People Who Received Childhood Vaccinia Vaccination
by Chris Davis, Jianmin Zuo, Rachel Bruton, Marie Hodges, Tom Roberts, Maria Manali, Paula Olmo, Brian Willett, Paul Moss and Helen Parry
Biology 2026, 15(3), 234; https://doi.org/10.3390/biology15030234 - 26 Jan 2026
Viewed by 514
Abstract
Monkeypox virus (MPXV) is a zoonotic Orthopoxvirus responsible for Monkeypox (Mpox), historically associated with sporadic zoonotic transmission but increasingly characterised by sustained human-to-human spread. While vaccinia-based vaccination is known to confer cross-protection against MPXV, the durability of such immunity over a human lifetime [...] Read more.
Monkeypox virus (MPXV) is a zoonotic Orthopoxvirus responsible for Monkeypox (Mpox), historically associated with sporadic zoonotic transmission but increasingly characterised by sustained human-to-human spread. While vaccinia-based vaccination is known to confer cross-protection against MPXV, the durability of such immunity over a human lifetime remains incompletely characterised. Here, we assessed humoral and cellular immune responses to MPXV in octogenarians and nonagenarians vaccinated against smallpox during childhood. Twenty-three adults aged 79–94 years (median 83), who self-reported childhood vaccinia vaccination between 1925 and 1940, were recruited. MPXV-specific antibody responses were evaluated using ELISA, targeting homologous vaccinia and MPXV proteins, and live-virus neutralisation assays. Cellular immunity was assessed by IFN-γ ELISpot following stimulation with peptide pools derived from highly conserved vaccinia antigens. Responses were also obtained from younger, recently MVA–BN-vaccinated and unvaccinated control donors. All historically vaccinated participants exhibited MPXV-reactive IgG responses, with antibody binding and neutralisation levels comparable to recently vaccinated individuals. Functional neutralising activity against MPXV was detected in all donors, with ≥50% neutralisation observed in 78% of participants. Antibody concentrations correlated strongly with neutralisation capacity. T-cell responses were detectable in all historically vaccinated donors, most prominently against the major core protein A10L, although reduced magnitudes were observed in participants over 90 years of age. No MPXV-specific humoral or cellular responses were detected in unvaccinated controls. These findings demonstrate that childhood vaccinia vaccination induces durable humoral and cellular immunity against MPXV persisting for over seven decades. Historical smallpox vaccination status may therefore remain a relevant determinant of protection against Mpox. Full article
(This article belongs to the Section Infection Biology)
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12 pages, 1194 KB  
Article
Strengthening the National Reference Laboratory in the Republic of Congo: An Investment Imperative for Tuberculosis Diagnostics
by Darrel Ornelle Elion Assiana, Franck Hardain Okemba-Okombi, Salomon Tchuandom Bonsi, Freisnel Hermeland Mouzinga, Juliet E. Bryant, Jean Akiana, Tanou Joseph Kalivogui, Alain Disu Kamalandua, Nuccia Saleri, Lionel Caruana, Hugues Traoré Asken and Dissou Affolabi
Trop. Med. Infect. Dis. 2026, 11(1), 23; https://doi.org/10.3390/tropicalmed11010023 - 13 Jan 2026
Cited by 1 | Viewed by 581
Abstract
National Tuberculosis Reference Laboratories (NTRLs) are central to tuberculosis (TB) control programs. Between 2018 and 2024, the Republic of Congo, a country of 6 million inhabitants, achieved a transformative strengthening of its TB diagnostic system, coordinated by the NTRL. Strategic investments, supported mainly [...] Read more.
National Tuberculosis Reference Laboratories (NTRLs) are central to tuberculosis (TB) control programs. Between 2018 and 2024, the Republic of Congo, a country of 6 million inhabitants, achieved a transformative strengthening of its TB diagnostic system, coordinated by the NTRL. Strategic investments, supported mainly by international partners, enabled a substantial decentralization of services, expanding the diagnostic network from 38 to 113 diagnostic and testing centers and increasing GeneXpert sites from 3 to 31. The expansion of the diagnostic network and specimen referral system was associated with a reduced structural gap in diagnostic coverage by extending access to GeneXpert testing to a larger number of peripheral and previously underserved centers. Critically, the establishment of a BSL-3 laboratory and the deployment of advanced assays like Xpert MTB/XDR ended the reliance on overseas testing by introducing in-country capacity for multidrug-resistant and pre-extensively drug-resistant TB detection. These systemic improvements were associated with significant positive outcomes, including an annual molecular testing surging from 11,609 in 2022 to over 27,000 in 2024 and bacteriological confirmation rates rising from 34 to 73%. This comprehensive laboratory systems strengthening, which also facilitated cross-programmatic initiatives like HIV and Mpox testing integration, underscores how sustained investment in infrastructure, logistics, and quality management is fundamental to improving case detection, surveillance, and progress toward the WHO End TB Strategy milestones. Full article
(This article belongs to the Special Issue Tuberculosis Diagnosis: Current, Ongoing and Future Approaches)
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8 pages, 1046 KB  
Article
UV-C Irradiation Effectiveness on Mpox-Virus-Contaminated Surfaces
by Anna Gidari, Samuele Sabbatini, Carlo Pallotto, Sabrina Bastianelli, Sara Pierucci, Chiara Busti, Giulia Proietti, Alessia Lai, Giuseppe Vittorio De Socio and Daniela Francisci
Pathogens 2026, 15(1), 78; https://doi.org/10.3390/pathogens15010078 - 10 Jan 2026
Viewed by 488
Abstract
Introduction: Mpox virus (MpoxV), an emerging zoonotic pathogen, has recently caused global concern due to increasing outbreaks beyond its traditional endemic regions. While transmission primarily occurs via close contact, fomites are also suspected of contributing. This study aims to evaluate the effectiveness of [...] Read more.
Introduction: Mpox virus (MpoxV), an emerging zoonotic pathogen, has recently caused global concern due to increasing outbreaks beyond its traditional endemic regions. While transmission primarily occurs via close contact, fomites are also suspected of contributing. This study aims to evaluate the effectiveness of UV-C irradiation on MpoxV-contaminated surfaces. Methods: the virucidal activity of UV-C (254 nm) irradiation on MpoxV applied to plastic, glass, and stainless-steel surfaces was assessed. Using a viral stock of 2.49 × 105 TCID50/mL, the samples were exposed to increasing UV-C doses. Viral titers were quantified through TCID50 and plaque assays. Results: A UV-C dose of 6.34 mJ/cm2 achieved a >2-log reduction of viral load, below the detection limit (31.6 TCID50/mL), on all tested surfaces. EC90 values were determined as 3.33 mJ/cm2 (plastic), 0.81 mJ/cm2 (stainless steel), and 1.98 mJ/cm2 (glass). No viable virus was detectable post-treatment at these doses on plastic and stainless steel while the titer was significantly reduced on glass. Conclusions: UV-C irradiation at low doses effectively inactivated MpoxV on various fomites. These findings support UV-C as a rapid and effective environmental disinfection strategy in healthcare and community settings to prevent indirect transmission of MpoxV. Full article
(This article belongs to the Section Viral Pathogens)
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7 pages, 312 KB  
Case Report
Mpox Clade IIb Virus Introduction into Kinshasa, Democratic Republic of the Congo, July 2025
by Tony Wawina-Bokalanga, Eddy Kinganda-Lusamaki, Christian Ngandu, Prince Akil-Bandali, Jérémie Kundey-Mafu, Nadege Ngombe, Laurens Liesenborghs, Princesse Paku-Tshambu, Lorenzo Subissi, Pauline-Chloé Muswamba-Kayembe, Samy Tessi-Mvutukulu, Jacques Santini-Mafuta, Gradi Luakanda-Ndelemo, Olga Ntumba-Tshitenge, Mory Keita, Israel Cinkobu-Bualukengu, Emmanuel Lokilo-Lofiko, Fiston Cikaya-Kankolongo, Sikoti Josaphat, Cris Kacita, Adelar Lofungola, Judith Tete-Sitra, Raphael Lumembe-Numbi, Elzedek Mabika-Bope, Adrienne Amuri-Aziza, Daan Jansen, Jean-Claude Makangara-Cigolo, Jeanine Nkakulu, Yap Boum, Ngashi Ngongo, Sofonias Tessema, Nick Loman, Áine O’Toole, Anne W. Rimoin, Pierre Akilimali, Nicole A. Hoff, Jason Kindrachuk, Steve Ahuka-Mundeke, Martine Peeters, Dieudonné Mwamba, Koen Vercauteren, Andrew Rambaut, Jean-Jacques Muyembe-Tamfum and Placide Mbala-Kingebeniadd Show full author list remove Hide full author list
Viruses 2026, 18(1), 87; https://doi.org/10.3390/v18010087 - 8 Jan 2026
Viewed by 828
Abstract
Clade I mpox virus (MPXV) is endemic in the Democratic Republic of the Congo (DRC). Recent studies have described the changing epidemiology of mpox in the country, which has been mainly characterized by the emergence of new MPXV lineages, Clade Ib/sh2023 and Ia/sh2024, [...] Read more.
Clade I mpox virus (MPXV) is endemic in the Democratic Republic of the Congo (DRC). Recent studies have described the changing epidemiology of mpox in the country, which has been mainly characterized by the emergence of new MPXV lineages, Clade Ib/sh2023 and Ia/sh2024, associated with sustained human-to-human transmission. Both Clade Ib/sh2023 and Ia/sh2024 are co-circulating in Kinshasa, the capital city of the DRC. Here, we report the first two cases of Clade IIb/sh2017 identified in Kinshasa, DRC, imported from West Africa and locally transmitted. Clinical specimens were collected and tested by PCR. We performed whole genome sequencing using a tiled-amplicon sequencing approach with Clade IIb MPXV-specific primers. The phylogenetic tree shows that Kinshasa Clade IIb MPXV is assigned to Clade IIb/sh2017 within the newly designated lineage G.1, as identified in January 2025 in Sierra-Leone. Full article
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17 pages, 1215 KB  
Review
Maternal–Fetal Implications of Mpox Infection: Current Evidence
by Stefany Silva Pereira, Antonio Braga, Beatriz Bussi Rosolen, Talita Almeida Durães, Marcela Fermoselle de Vita Silva, Giovanna Alves de Britto, Giuliana Augustinelli Sales, Gustavo Yano Callado, Camilla Martins dos Santos Maia, Evelyn Traina, Edward Araujo Júnior, Gabriele Tonni and Roberta Granese
J. Clin. Med. 2026, 15(1), 399; https://doi.org/10.3390/jcm15010399 - 5 Jan 2026
Viewed by 629
Abstract
Mpox is an emerging zoonotic infection caused by the Monkeypox virus, an Orthopoxvirus with increasing global relevance following the 2022 multinational outbreak. Historically endemic to Central and West Africa, the disease has evolved from sporadic zoonotic transmission to sustained human-to-human spread, particularly through [...] Read more.
Mpox is an emerging zoonotic infection caused by the Monkeypox virus, an Orthopoxvirus with increasing global relevance following the 2022 multinational outbreak. Historically endemic to Central and West Africa, the disease has evolved from sporadic zoonotic transmission to sustained human-to-human spread, particularly through close physical and intimate contact. Clinical manifestations typically include fever, lymphadenopathy, and progressive mucocutaneous lesions, although severity varies according to viral clade, immune status, and comorbidities. The 2022 outbreak, predominantly associated with the Clade IIb variant, was characterized by milder disease, localized lesions, and reduced mortality compared with the more virulent Clade I variant. Despite this, severe outcomes remain possible, particularly in vulnerable groups such as children, pregnant individuals, immunocompromised patients, and persons with extensive dermatological disorders. Diagnosis relies primarily on polymerase chain reaction testing from lesion-derived samples, with genomic sequencing serving as a complementary tool for epidemiological surveillance. Management is largely supportive, though antivirals such as tecovirimat may be considered in severe cases or in high-risk populations. Data regarding therapeutic safety in pregnancy are limited; however, tecovirimat appears to have the most favorable profile, whereas cidofovir and brincidofovir remain contraindicated. Prevention strategies include targeted vaccination with the non-replicating Modified Vaccinia Ankara–Bavarian Nordic vaccine, used for both pre- and post-exposure prophylaxis, particularly in individuals at elevated risk. Given the evolving epidemiological profile, the potential for vertical transmission, and the risk of adverse perinatal outcomes, Mpox infection during pregnancy poses unique clinical challenges. This review synthesizes current evidence on virology, clinical presentation, diagnosis, prevention, and management, with an emphasis on obstetric considerations and public health implications. Full article
(This article belongs to the Special Issue Clinical Updates on Maternal Fetal Medicine: 2nd Edition)
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26 pages, 3426 KB  
Review
The Emerging Threat of Monkeypox: An Updated Overview
by Galal Yahya, Nashwa H. Mohamed, Al-Hassan Soliman Wadan, Esteban M. Castro, Amira Kamel, Ahmed A. Abdelmoaty, Maha E. Alsadik, Luis Martinez-Sobrido and Ahmed Mostafa
Viruses 2026, 18(1), 69; https://doi.org/10.3390/v18010069 - 3 Jan 2026
Viewed by 1388
Abstract
Monkeypox (MPOX) is an emerging zoonotic disease caused by monkeypox virus (MPXV), an orthopoxvirus closely related to smallpox. Initially confined to endemic regions in Central and West Africa, MPOX has recently gained global significance with outbreaks reported across multiple continents. MPXV is maintained [...] Read more.
Monkeypox (MPOX) is an emerging zoonotic disease caused by monkeypox virus (MPXV), an orthopoxvirus closely related to smallpox. Initially confined to endemic regions in Central and West Africa, MPOX has recently gained global significance with outbreaks reported across multiple continents. MPXV is maintained in animal reservoirs but is increasingly transmitted from person to person, facilitated by close contact, respiratory droplets, and, in some cases, sexual transmission. Clinically, MPOX presents with fever, lymphadenopathy, and a characteristic vesiculopustular rash, though atypical manifestations have been observed in recent outbreaks, complicating diagnosis. Laboratory confirmation relies on molecular testing, while differential diagnosis must consider varicella, herpes, and other vesicular illnesses. Therapeutic options remain limited; supportive care is the cornerstone of management, but antivirals such as tecovirimat and brincidofovir, as well as smallpox vaccines, have shown efficacy in mitigating disease severity and preventing infection. The unprecedented global outbreak has underscored the importance of surveillance, rapid diagnostics, and coordinated public health responses to contain transmission. This review provides an overview of epidemiology, virology, clinical manifestations, modes of transmission, available diagnostics, and prophylactic and therapeutic strategies against MPOX. We also discuss the role of animal reservoirs, viral evolution, and human-to-human transmission in shaping the dynamics of recent MPOX outbreaks. By summarizing the latest evidence, this review aims to inform clinicians, researchers, and policymakers about key aspects of MPOX biology, clinical management, and prevention, while identifying gaps that warrant future investigation for the control of this and potentially other emerging zoonotic-related pathogens with an impact on human health. Full article
(This article belongs to the Special Issue Emerging and Re-Emerging Viral Zoonoses)
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19 pages, 3714 KB  
Article
Unveiling Intra-Clonal Diversity of Monkeypox Virus from Brazil’s First Outbreak Wave
by Amanda Stéphanie Arantes Witt, João Victor Rodrigues Pessoa Carvalho, Izabela Mamede, Talita Emile Ribeiro Adelino, Felipe Campos de Melo Iani, Maurício Teixeira Lima, Thalita Souza Arantes, Denilson Eduardo Silva Cunha, Rodrigo Araújo Lima Rodrigues, Giliane de Souza Trindade, Erna Geessien Kroon, Nidia Esther Colquehuanca Arias, Glória Regina Franco and Jônatas Santos Abrahão
Viruses 2026, 18(1), 62; https://doi.org/10.3390/v18010062 - 31 Dec 2025
Viewed by 703
Abstract
The monkeypox virus (MPXV) is an emerging zoonotic pathogen responsible for mpox, a disease characterized by some smallpox-like symptoms, typically mild but occasionally fatal. The largest mpox recorded global outbreak began in May 2022, with over 162,000 cases across 140 countries. Herein, we [...] Read more.
The monkeypox virus (MPXV) is an emerging zoonotic pathogen responsible for mpox, a disease characterized by some smallpox-like symptoms, typically mild but occasionally fatal. The largest mpox recorded global outbreak began in May 2022, with over 162,000 cases across 140 countries. Herein, we have analyzed the intra-clonal diversity of MPXV obtained from a single skin lesion sample from a male patient (June 2022). Three viral clones were obtained following phenotypic evaluation of MPXV lysis plaque characteristics over a three-course infection in BSC-40 cells. Unlike the vaccinia virus Western Reserve (VACV-WR) strain, MPXV clones did not produce comet-like structures, suggesting reduced extracellular enveloped virus (EEV) morphotype release, which is associated with viral dissemination. Whole-genome sequencing and assembly identified subtle differences among clones. Comparative genomic analyses, including synteny and single nucleotide variation (SNV) calling, revealed intra-clonal differences and divergence from clade I and II references, although the variety of mutations found did not reveal possible variations at the protein level. Altogether, these findings suggest that although similar, it is possible that distinct MPXV variants may circulate together and can be found in a single exanthematous lesion. Full article
(This article belongs to the Special Issue Nucleocytoviricota)
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16 pages, 1613 KB  
Review
Mpox in People Living with HIV: Clinical Challenges, Preventive Strategies and Public Health Implications
by Rita Cordeiro, João Caria, Daniel Sobral and Diana Póvoas
Viruses 2025, 17(12), 1558; https://doi.org/10.3390/v17121558 - 28 Nov 2025
Viewed by 814
Abstract
Monkeypox virus (MPXV) re-emerged in 2022 with a global outbreak that affected more than 100,000 individuals worldwide. People living with HIV (PLWH) accounted for a substantial proportion of cases, raising concerns about disease presentation, management, and outcomes in this population. Evidence indicates that [...] Read more.
Monkeypox virus (MPXV) re-emerged in 2022 with a global outbreak that affected more than 100,000 individuals worldwide. People living with HIV (PLWH) accounted for a substantial proportion of cases, raising concerns about disease presentation, management, and outcomes in this population. Evidence indicates that PLWH with advanced or uncontrolled HIV infection experienced more severe mpox, with higher hospitalization rates, more complications, and longer disease courses. In contrast, individuals with well-controlled HIV generally had outcomes similar to those without HIV. Access to timely diagnosis, consistent antiretroviral therapy, and availability of tecovirimat were key factors influencing prognosis. Reports also suggest bidirectional interactions between mpox and HIV pathogenesis. Immune activation and APOBEC3-related viral evolution have been proposed; however, these mechanisms remain incompletely characterized and warrant further investigation. Moreover, disparities in healthcare access and stigma compound the vulnerability of PLWH, emphasizing the need for integrated approaches. Full article
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16 pages, 1495 KB  
Article
Molecular Aspects of the Emergence of Monkeypox Virus Clades
by Igor V. Babkin, Irina N. Babkina and Nina V. Tikunova
Viruses 2025, 17(12), 1549; https://doi.org/10.3390/v17121549 - 26 Nov 2025
Viewed by 806
Abstract
Monkeypox virus (MPXV), which previously caused mainly zoonotic infections, is currently the causative agent of the mpox outbreak that began in 2022. Since the mpox outbreak is characterized by sustained human-to-human transmission, the evolutionary trajectory of MPXV is an important scientific issue. The [...] Read more.
Monkeypox virus (MPXV), which previously caused mainly zoonotic infections, is currently the causative agent of the mpox outbreak that began in 2022. Since the mpox outbreak is characterized by sustained human-to-human transmission, the evolutionary trajectory of MPXV is an important scientific issue. The prevailing hypothesis suggests that the modern orthopoxviruses originated from cowpox-like ancestors with larger genomes that infected a wide range of hosts. Subsequent evolution included the reduction of the genome and the accumulation of substitutions in key proteins. Molecular dating of MPXV evolution revealed 5–6-fold acceleration in the evolutionary rate that was observed in subclade IIb after 2018, reaching 1.8 × 10−5 substitutions/site/year, likely due to virus’ adaptation to humans. The origin of MPXV from its precursor was primarily driven by the accumulation of non-synonymous substitutions in the key host range genes, including those associated with the protein inhibiting host protein synthesis (OPG173) and host immune evasion (OPG027). The subsequent divergence of MPXV into clades I and II largely depended on mutations in the gene encoding the Bcl-2-like protein. Finally, the division of clade II into subclades IIa and IIb was facilitated by further non-synonymous substitutions in the soluble interferon alpha/beta receptor and hemagglutinin genes. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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23 pages, 1946 KB  
Review
Natural Product-Based Drug Discovery for Monkeypox Virus: Integrating In Silico Approaches and Therapeutic Development Strategies
by Aganze Gloire-Aimé Mushebenge and David Ditaba Mphuthi
Future Pharmacol. 2025, 5(4), 69; https://doi.org/10.3390/futurepharmacol5040069 - 26 Nov 2025
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Abstract
The global spread of Monkeypox virus (MPXV) has emerged as a major public health concern, with the 2022 outbreak underscoring the urgent need for effective antiviral therapies. Current treatment options are limited because no drugs specifically target Mpox, and existing recommendations rely on [...] Read more.
The global spread of Monkeypox virus (MPXV) has emerged as a major public health concern, with the 2022 outbreak underscoring the urgent need for effective antiviral therapies. Current treatment options are limited because no drugs specifically target Mpox, and existing recommendations rely on repurposed smallpox antivirals that may cause resistance. This highlights the critical need for novel therapeutic agents targeting key viral and host factors involved in MPXV pathogenesis. Medicinal plants provide a rich reservoir of bioactive compounds with potential antiviral activity, particularly in low- and middle-income countries where they play an essential role in healthcare. To address this issue, we conducted a review exploring innovative in silico approaches for natural product-based drug discovery against MPXV. Computational studies identified phytochemicals such as curcumin, punicalagin, rosmarinic acid, and quercitrin with strong affinities for key viral proteins including DNA polymerase, TMPK, DdRp, A42R, MTase, p37, and envelope proteins and favorable pharmacokinetic profiles Despite these promising findings, fragmented biological datasets, viral mutability, and limited in vitro and in vivo validation hinder clinical translation. Our analysis highlights integrating AI-driven virtual screening with experimental validation to accelerate MPXV drug discovery, providing a scalable framework for managing emerging viral threats. Full article
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