The fitness of molnupiravir-signed SARS-CoV-2 variants: imputation analysis based on prescription counts and GISAID analyses by country.

IF 3.2 4区医学 Q3 VIROLOGY

Intervirology Pub Date : 2024-11-08 DOI:10.1159/000540282

Daniele Focosi, Dave McNally, Fabrizio Maggi

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引用次数: 0

Abstract

Introduction: Molnupiravir is one of the oral direct-acting antivirals against SARS-CoV-2, largely deployed during the COVID-19 pandemic since the 2022 Omicron wave. While efficacy has been questioned in post-marketing clinical trials (leading to the EMA withdrawing its authorization), growing concerns have mounted regarding its possible mutagenic effects on the virus. While it has been assumed that either all the host viral load was cleared by the drug or that drug-generated variants were not fit enough to survive, several lineages with a high transition/transversion ratio (a signature of molnupiravir action) have been recently reported from GISAID.

Methods: We report here a systematic analysis of the GISAID database for sequences showing a molnupiravir signature, exposing a public web-based interface (https://ukcovid.xyz/molnupiravir/ ), and performing an imputation analysis based on per-country prescription (corrected by sequencing).

Results: Our analysis confirms a direct correlation between the number of molnupiravir courses and the number of mutationally signed deposited in GISAID in individual countries.

Conclusions: Molnupiravir can generate fit SARS-CoV-2 variants that transmit in the general population.

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molnupiravir签名SARS-CoV-2变体的适应性：基于处方数的估算分析和按国家分列的GISAID分析。

简介莫能吡韦是抗击 SARS-CoV-2 的口服直接作用抗病毒药物之一，自 2022 年 Omicron 疫潮以来，在 COVID-19 大流行期间主要使用莫能吡韦。虽然在上市后的临床试验中疗效受到质疑（导致欧洲药品管理局撤销其授权），但人们越来越担心它对病毒可能产生的诱变作用。人们一直认为，要么是药物清除了所有宿主病毒载量，要么是药物产生的变异体不足以存活，但最近 GISAID 报告了几种具有高过渡/转化比（molnupiravir 作用的标志）的病毒系：我们在此报告对GISAID数据库中显示出molnupiravir特征的序列进行了系统分析，并公开了一个基于网络的界面（https://ukcovid.xyz/molnupiravir/ ），还根据各国处方（通过测序校正）进行了估算分析：结果：我们的分析证实，各个国家的莫仑吡韦疗程数与存入 GISAID 的变异签名数之间存在直接关联：结论：莫鲁吡拉韦能产生适合在普通人群中传播的 SARS-CoV-2 变异株。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Intervirology 医学-病毒学

CiteScore

5.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Intervirology'' covers progress in both basic and clinical virus research, and aims to provide a forum for the various disciplines within virology. Issues publishing original papers alternate with thematic issues, focusing on clearly defined topics. This thematic concentration serves to make timely reviews, research reports and controversy easily accessible to both specialists in the field and those who want to keep track of the latest developments outside their own area of interest. In addition to original papers, regular issues publish short communications and letters to the editor to provide readers with a forum for the exchange of ideas and comments. The scope encompasses work on the molecular biology of human and animal viruses, including genome organization and regulation, and the structure and function of viral proteins. The pathogenesis, immunology, diagnosis, epidemiology, prophylaxis and therapy of viral diseases are considered.