Department of Microbiology, Sant Gadge Baba Amravati University (SGBAU), Amravati, Maharashtra, India.
Division of Surgical Research/Rhode Island Hospital, Brown University, Providence, Rhode Island, USA.
Drugs Today (Barc). 2022 Jul;58(7):335-350. doi: 10.1358/dot.2022.58.7.3419558.
Molnupiravir (MK-4482, EIDD-2801) is a promising broad-spectrum experimental antiviral developed by Merck & Co. It is a nucleoside analogue prodrug that undergoes rapid conversion into nucleoside triphosphate (NTP) by intracellular metabolic processes. NTP inhibits viral polymerase by acting as an alternative substrate. Molnupiravir was initially developed to treat influenza and Venezuelan equine encephalitis virus (VEEV) infection as it exerts its antiviral activity by inhibiting RNA-dependent RNA polymerase (RdRp). Currently, it is being developed for the treatment of SARS-CoV-2 infection. Molnupiravir has demonstrated potent in vitro antiviral activity against positive-sense RNA viruses including influenza viruses, SARS-CoV, SARS-CoV-2 and MERS-CoV with low cytotoxicity and a high resistance barrier. Molnupiravir has been evaluated in phase I, II and III trials where it has demonstrated good efficacy, dose-dependent pharmacokinetics and a sound safety profile. In an interim analysis of a phase III study, treatment with molnupiravir reduced the risk of hospitalization or death by 50% in patients with COVID-19; in the final analysis, the reduction was 30%. On the basis of positive results in clinical trials, molnupiravir has been authorized for emergency use by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) and the U.S. Food and Drug Administration (FDA) in adults with mild to moderate COVID-19.
莫努匹韦（MK-4482，EIDD-2801）是由默克公司开发的一种有前途的广谱实验性抗病毒药物。它是一种核苷类似物前药，通过细胞内代谢过程迅速转化为核苷三磷酸（NTP）。NTP 通过充当替代底物来抑制病毒聚合酶。莫努匹韦最初是为治疗流感和委内瑞拉马脑炎病毒（VEEV）感染而开发的，因为它通过抑制 RNA 依赖性 RNA 聚合酶（RdRp）发挥抗病毒活性。目前，它正在开发用于治疗 SARS-CoV-2 感染。莫努匹韦已在体外显示出对包括流感病毒、SARS-CoV、SARS-CoV-2 和 MERS-CoV 在内的正链 RNA 病毒的强大抗病毒活性，具有低细胞毒性和高耐药屏障。莫努匹韦已在 I、II 和 III 期试验中进行了评估，结果表明其具有良好的疗效、剂量依赖性药代动力学和良好的安全性。在 III 期研究的中期分析中，莫努匹韦治疗可使 COVID-19 患者住院或死亡的风险降低 50%；在最终分析中，降低了 30%。基于临床试验的阳性结果，莫努匹韦已获得英国药品和保健品管理局（MHRA）和美国食品和药物管理局（FDA）的紧急使用授权，用于治疗轻中度 COVID-19 的成年人。
