Molnupiravir, a prodrug of the nucleoside derivative β-D- N 4 -hydroxycytidine (NHC), is currently in clinical trials for COVID-19 therapy. However, the biochemical mechanisms involved in molnupiravir-induced mutagenesis had not been explored. In a recent study, Gordon et al. demonstrated that NHC can be incorporated into viral RNA and subsequently extended and used as template for RNA-dependent RNA synthesis, proposing a mutagenesis model consistent with available virological evidence. Their study uncovers molecular mechanisms by which molnupiravir drives SARS-CoV-2 into error catastrophe.
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【저자키워드】 COVID-19, SARS-CoV-2, molnupiravir, antiviral drug, SARS-CoV, severe acute respiratory syndrome coronavirus, MERS-CoV, Middle East respiratory syndrome coronavirus, RNA polymerase, lethal mutagenesis, COVID-19, coronavirus infectious disease 2019, NHC, β-D-N 4-hydroxycytidine, RdRp, RNA-dependent RNA polymerase, rNTP, ribonucleoside triphosphate, 【초록키워드】 clinical trial, therapy, molnupiravir, clinical trials, molecular mechanism, NHC, Viral, Viral RNA, COVID-19 therapy, mechanism, prodrug, Mutagenesis, Template, biochemical, RNA synthesis, molecular mechanisms, nucleoside, Virological evidence, involved, demonstrated, 【제목키워드】 Mutagenesis,
【저자키워드】 COVID-19, SARS-CoV-2, molnupiravir, antiviral drug, SARS-CoV, severe acute respiratory syndrome coronavirus, MERS-CoV, Middle East respiratory syndrome coronavirus, RNA polymerase, lethal mutagenesis, COVID-19, coronavirus infectious disease 2019, NHC, β-D-
뉴클레오사이드 유도체인 β-D-N 4 -하이드록시시티딘(NHC)의 전구약물인 몰누피라비르(Molnupiravir)는 현재 COVID-19 치료법에 대한 임상 시험이 진행 중입니다. 그러나, 몰누피라비르에 의한 돌연변이 유발과 관련된 생화학적 기전은 탐구되지 않았다. 최근 연구에서 Gordon et al. NHC가 바이러스 RNA에 통합되고 이어서 확장되어 RNA 의존성 RNA 합성을 위한 주형으로 사용될 수 있음을 보여주었으며, 이용 가능한 바이러스학적 증거와 일치하는 돌연변이 유발 모델을 제안했습니다. 그들의 연구는 몰누피라비르가 SARS-CoV-2를 오류 재앙으로 몰아가는 분자 메커니즘을 밝혀냈습니다.