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莫努匹韦:一种针对快速突变的严重急性呼吸综合征冠状病毒 2 的致命诱变药物——叙事性综述。

Molnupiravir: A lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2-A narrative review.

机构信息

Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Warmadewa, Denpasar, Indonesia.

Department of Internal Medicine, Sanjiwani Hospital, Gianyar, Indonesia.

出版信息

J Med Virol. 2022 Jul;94(7):3006-3016. doi: 10.1002/jmv.27730. Epub 2022 Apr 2.

DOI:10.1002/jmv.27730
PMID:35315098
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9088670/
Abstract

Broad-spectrum antiviral agents targeting viral RNA-dependent RNA polymerase (RdRp) are expected to be a key therapeutic strategy in the ongoing coronavirus disease 2019 (COVID-19) pandemic and its future variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Molnupiravir is a nucleoside analog that in vivo experiments have been reported to inhibit the replication of SARS-CoV-2, the virus that causes COVID-19. Clinical trials of molnupiravir as a therapy for patients with mild-to-moderate COVID-19 also suggest its significant therapeutic efficacy in comparison to placebo. Molnupiravir is lethally mutagenic against viral RNA, but its effect on host cell DNA is being questioned. Herein, the safety concerns of molnupiravir are discussed with recent findings from published reports and clinical trials. The unchanged efficacy of molnupiravir against mutated SARS-CoV-2 variants is also highlighted. With its administration via the oral route, molnupiravir is expected to turn the tide of the COVID-19 pandemic.

摘要

广谱抗病毒药物靶向病毒 RNA 依赖性 RNA 聚合酶(RdRp),有望成为应对当前 2019 年冠状病毒病(COVID-19)大流行及其未来严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)变异株的关键治疗策略,SARS-CoV-2 是引发 COVID-19 的病毒。莫努匹韦是一种核苷类似物,据报道体内实验可抑制引发 COVID-19 的 SARS-CoV-2 的复制。莫努匹韦作为治疗轻症至中度 COVID-19 患者的临床试验也表明,与安慰剂相比,其具有显著的治疗效果。莫努匹韦对病毒 RNA 具有致死性诱变作用,但对宿主细胞 DNA 的影响仍存在争议。本文讨论了莫努匹韦的安全性问题,并结合已发表的报告和临床试验的最新发现进行了分析。还强调了莫努匹韦对突变的 SARS-CoV-2 变异株仍保持疗效不变的特性。莫努匹韦通过口服途径给药,有望改变 COVID-19 大流行的局面。

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Acceptance of COVID-19 vaccination at different hypothetical efficacy and safety levels in ten countries in Asia, Africa, and South America.亚洲、非洲和南美洲十个国家对不同假设效力和安全水平的新冠疫苗的接受情况。
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Phase 2/3 Trial of Molnupiravir for Treatment of Covid-19 in Nonhospitalized Adults.Molnupiravir 治疗非住院成人 COVID-19 的 2/3 期试验。
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Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19.莫努匹拉韦或安慰剂用于新冠肺炎住院患者的随机试验
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