Molnupiravir increases SARS‐CoV‐2 genome diversity and complexity: A case‐control cohort study
Cesare Ernesto Maria Gruber, Fabio Giovanni Tucci, Emanuela Giombini, Valentina Mazzotta, Pietro Giorgio Spezia, Martina Rueca, Ilaria Mastrorosa, Lavinia Fabeni, Giulia Berno, Ornella Butera, Silvia Rosati, Eliana Specchiarello, Fabrizio Carletti, Daniele Focosi, Emanuele Nicastri, Enrico Girardi, Andrea Antinori, Fabrizio Maggi
Journal of Medical Virology, doi:10.1002/jmv.29642
Molnupiravir, an oral direct-acting antiviral effective in vitro against SARS-CoV-2, has been largely employed
effective transmission of newly drug-induced possibly emerging variants. In conclusions, our data confirm the suspect that molnupiravir-generated variants can be generated also in immunocompetent outpatients 33 and highlight the importance of genomic surveillance in the characterization of new, potentially transmissible drug-derived variants.
AUTHOR CONTRIBUTIONS Cesare Ernesto Maria Gruber, Emanuela Giombini, Martina Rueca, and Daniele Focosi conceived the study and developed the study protocol. Enrico Girardi and Fabrizio Maggi provided oversight and supervision. Martina Rueca, Lavinia Fabeni, Giulia Berno, Ornella Butera, Eliana Specchiarello, and Fabrizio Carletti did the molecular assays and sequencing. Valentina Mazzotta, Ilaria Mastrorosa, Silvia Rosati, Emanuele Nicastri, and Andrea Antinori collected the clinical data. Fabio Giovanni Tucci, Emanuela Giombini, and Cesare Ernesto Maria Gruber did the bioinformatic analyses of the data. Cesare Ernesto Maria Gruber, Emanuela Giombini, and Fabio Giovanni Tucci wrote the original draft of the manuscript. Fabrizio Maggi, Andrea Antinori, and Daniele Focosi critically reviewed the manuscript. All authors had access to the data in the study and were ultimately responsible for deciding to submit it for publication.
CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest.
ETHICS STATEMENT The study was conducted in accordance with the Declaration of
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'abstract': '<jats:title>Abstract</jats:title><jats:p>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\xa0(GISAID) and International Nucleotide Sequence Database '
'Collaboration\xa0(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.</jats:p>',
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