{"title":"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。","authors":"Daniele Focosi, Dave McNally, Fabrizio Maggi","doi":"10.1159/000540282","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>Our analysis confirms a direct correlation between the number of molnupiravir courses and the number of mutationally signed deposited in GISAID in individual countries.</p><p><strong>Conclusions: </strong>Molnupiravir can generate fit SARS-CoV-2 variants that transmit in the general population.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The fitness of molnupiravir-signed SARS-CoV-2 variants: imputation analysis based on prescription counts and GISAID analyses by country.\",\"authors\":\"Daniele Focosi, Dave McNally, Fabrizio Maggi\",\"doi\":\"10.1159/000540282\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>Our analysis confirms a direct correlation between the number of molnupiravir courses and the number of mutationally signed deposited in GISAID in individual countries.</p><p><strong>Conclusions: </strong>Molnupiravir can generate fit SARS-CoV-2 variants that transmit in the general population.</p>\",\"PeriodicalId\":14547,\"journal\":{\"name\":\"Intervirology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-11-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Intervirology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000540282\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"VIROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Intervirology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000540282","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"VIROLOGY","Score":null,"Total":0}
The fitness of molnupiravir-signed SARS-CoV-2 variants: imputation analysis based on prescription counts and GISAID analyses by country.
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.
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.
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