tetano
Editor, Senior Moderator
J Med Virol
. 2024 May;96(5):e29642.
doi: 10.1002/jmv.29642.
Molnupiravir increases SARS-CoV-2 genome diversity and complexity: A case-control cohort study
Cesare Ernesto Maria Gruber 1 , Fabio Giovanni Tucci 2 , Emanuela Giombini 1 , Valentina Mazzotta 3 , Pietro Giorgio Spezia 1 , Martina Rueca 1 , Ilaria Mastrorosa 3 , Lavinia Fabeni 1 , Giulia Berno 1 , Ornella Butera 4 , Silvia Rosati 3 , Eliana Specchiarello 1 , Fabrizio Carletti 1 , Daniele Focosi 5 , Emanuele Nicastri 3 , Enrico Girardi 6 , Andrea Antinori 3 , Fabrizio Maggi 1
Affiliations
PMID: 38708812 DOI: 10.1002/jmv.29642
Abstract
Molnupiravir, an oral direct-acting antiviral effective in vitro against SARS-CoV-2, has been largely employed during the COVID-19 pandemic, since December 2021. After marketing and widespread usage, a progressive increase in SARS-CoV-2 lineages characterized by a higher transition/transversion ratio, a characteristic signature of molnupiravir action, appeared in the Global Initiative on Sharing All Influenza Data (GISAID) and International Nucleotide Sequence Database Collaboration (INSDC) databases. Here, we assessed the drug effects by SARS-CoV-2 whole-genome sequencing on 38 molnupiravir-treated persistently positive COVID-19 outpatients tested before and after treatment. Seventeen tixagevimab/cilgavimab-treated outpatients served as controls. Mutational analyses confirmed that SARS-CoV-2 exhibits an increased transition/transversion ratio seven days after initiation of molnupiravir. Moreover we observed an increased G->A ratio compared to controls, which was not related to apolipoprotein B mRNAediting enzyme, catalytic polypeptide-like (APOBEC) activity. In addition, we demonstrated for the first time an increased diversity and complexity of the viral quasispecies.
Keywords: SARS‐CoV‐2; complexity; diversity; molnupiravir; quasispecies; tixagevimab/cilgavimab; transition; transversion.
. 2024 May;96(5):e29642.
doi: 10.1002/jmv.29642.
Molnupiravir increases SARS-CoV-2 genome diversity and complexity: A case-control cohort study
Cesare Ernesto Maria Gruber 1 , Fabio Giovanni Tucci 2 , Emanuela Giombini 1 , Valentina Mazzotta 3 , Pietro Giorgio Spezia 1 , Martina Rueca 1 , Ilaria Mastrorosa 3 , Lavinia Fabeni 1 , Giulia Berno 1 , Ornella Butera 4 , Silvia Rosati 3 , Eliana Specchiarello 1 , Fabrizio Carletti 1 , Daniele Focosi 5 , Emanuele Nicastri 3 , Enrico Girardi 6 , Andrea Antinori 3 , Fabrizio Maggi 1
Affiliations
PMID: 38708812 DOI: 10.1002/jmv.29642
Abstract
Molnupiravir, an oral direct-acting antiviral effective in vitro against SARS-CoV-2, has been largely employed during the COVID-19 pandemic, since December 2021. After marketing and widespread usage, a progressive increase in SARS-CoV-2 lineages characterized by a higher transition/transversion ratio, a characteristic signature of molnupiravir action, appeared in the Global Initiative on Sharing All Influenza Data (GISAID) and International Nucleotide Sequence Database Collaboration (INSDC) databases. Here, we assessed the drug effects by SARS-CoV-2 whole-genome sequencing on 38 molnupiravir-treated persistently positive COVID-19 outpatients tested before and after treatment. Seventeen tixagevimab/cilgavimab-treated outpatients served as controls. Mutational analyses confirmed that SARS-CoV-2 exhibits an increased transition/transversion ratio seven days after initiation of molnupiravir. Moreover we observed an increased G->A ratio compared to controls, which was not related to apolipoprotein B mRNAediting enzyme, catalytic polypeptide-like (APOBEC) activity. In addition, we demonstrated for the first time an increased diversity and complexity of the viral quasispecies.
Keywords: SARS‐CoV‐2; complexity; diversity; molnupiravir; quasispecies; tixagevimab/cilgavimab; transition; transversion.