ArticleJournal of autoimmunity2022
Mutations in the monkeypox virus replication complex: Potential contributing factors to the 2022 outbreak.
Article in Journal of autoimmunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 76 citations in OpenAlex.
- Structure prediction and drug screening targeting monkeypox virus polymerase and surface proteins.Journal of computer-aided molecular design · 2026Article
- Exploration of the protein and pharmacological landscape of monkeypox virus treatment: from entry point to end point.Molecular diversity · 2026Review
- Therapeutic Innovations for Monkeypox Inhibition.International journal of molecular sciences · 2026Review
- Monkeypox (Mpox): a comprehensive review of epidemiology, therapeutic advances, and public health implications.Journal of health, population, and nutrition · 2026Review
- Emerging threats of monkeypox virus in 2024: current insights and future directions.Future science OA · 2025Review
- Understanding the evolutionary dynamics of Monkeypox virus through less explored pathways.Scientific reports · 2025Article
- A review of epidemiology, diagnosis, and management of Mpox: The role of One Health.Global health & medicine · 2025Review
- "Mpox in MSM: Tackling stigma, minimizing risk factors, exploring pathogenesis, and treatment approaches".Biomedical journal · 2025Review
- Mpox: An emerging or re-emerging infection with a potential colossal burden on healthcare globally.African journal of laboratory medicine · 2025Review
- Genomic variability and immunological aspects involved in response to MPXV infection.Frontiers in pharmacology · 2025Review
- The resurgence of monkeypox: Epidemiology, clinical features, and public health implications in the post-smallpox eradication era.New microbes and new infections · 2024Review
- Review
- Identification of the myxobacterial secondary metabolites Aurachin A and Soraphinol A as promising inhibitors of thymidylate kinase of the Monkeypox virus.Molecular diversity · 2024Article
- Epidemiology, Virology, and Mutation Landscape of Monkeypox Virus From Past to Present.Cureus · 2024Review
- Prediction of potential public health risk of the recent multicountry monkeypox outbreak: An update after the end declaration of global public health emergency.Health science reports · 2024Article
- Synergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection.Nature communications · 2024Article
- Structural insight into the assembly and working mechanism of helicase-primase D5 from Mpox virus.Nature structural & molecular biology · 2024Article
- Mpox (formerly monkeypox): pathogenesis, prevention, and treatment.Signal transduction and targeted therapy · 2023Review
- Exploring the key genomic variation in monkeypox virus during the 2022 outbreak.BMC genomic data · 2023Article
- Missing subunits of Mpox replication complex: Possible impact on structural organization.The Journal of infection · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Attributes contributing to the current monkeypox virus (MPXV) outbreak remain unknown. It has been established that mutations in viral proteins may alter phenotype and pathogenicity. To assess if mutations in the MPXV DNA replication complex (RC) contribute to the outbreak, we conducted a temporal analysis of available MPXV sequences to identify mutations, generated a DNA replication complex (RC) using structures of related viral and eukaryotic proteins, and structure prediction method AlphaFold. Ten mutations within the RC were identified and mapped onto the RC to infer role of mutations. Two mutations in F8L (RC catalytic subunit), and two in G9R (a processivity factor) were ∼100% prevalent in the 2022 sequences. F8L mutation L108F emerged in 2022, whereas W411L emerged in 2018, and persisted in 2022. L108 is topologically located to enhance DNA binding affinity of F8L. Therefore, mutation L108F can change the fidelity, sensitivity to nucleoside inhibitors, and processivity of F8L. Surface exposed W411L likely affects the binding of regulatory factor(s). G9R mutations S30L and D88 N in G9R emerged in 2022, and may impact the interaction of G9R with E4R (uracil DNA glycosylase). The remaining six mutations that appeared in 2001, reverted to the first (1965 Rotterdam) isolate. Two nucleoside inhibitors brincidofovir and cidofovir have been approved for MPXV treatment. Cidofovir resistance in vaccinia virus is achieved by A314T and A684V mutations. Both A314 and A684 are conserved in MPXV. Therefore, resistance to these drugs in MPXV may arise through similar mechanisms.
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