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Updated: Jun 27, 2025

Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
Published on: June 16, 2011
Molnupiravir increases SARS-CoV-2 genome diversity and complexity: A case-control cohort study
Cesare Ernesto Maria Gruber1, Fabio Giovanni Tucci2, Emanuela Giombini1
1Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.
Molnupiravir treatment increased SARS-CoV-2 mutations, specifically a higher transition/transversion ratio and G->A changes, indicating drug activity. This antiviral also increased viral quasispecies diversity in COVID-19 patients.
Area of Science:
- Virology
- Pharmacology
- Genomics
Background:
- Molnupiravir is an oral antiviral used against SARS-CoV-2.
- Post-marketing surveillance revealed SARS-CoV-2 lineages with increased transition/transversion ratios, a known molnupiravir signature.
Purpose of the Study:
- To assess the mutational effects of molnupiravir on SARS-CoV-2 in patients.
- To investigate the impact of molnupiravir on viral quasispecies diversity.
Main Methods:
- Whole-genome sequencing of SARS-CoV-2 from molnupiravir-treated patients.
- Comparative analysis with a control group treated with tixagevimab/cilgavimab.
- Mutational analysis focusing on transition/transversion ratios and G->A changes.
Main Results:
- Molnupiravir treatment led to a significantly increased transition/transversion ratio in SARS-CoV-2 seven days post-initiation.
- An elevated G->A mutation rate was observed, independent of APOBEC activity.
- Increased diversity and complexity of viral quasispecies were demonstrated.
Conclusions:
- Molnupiravir induces characteristic mutational signatures in SARS-CoV-2.
- The drug's impact extends to increased viral genetic diversity.
- Findings provide insights into molnupiravir's in vivo antiviral activity and potential evolutionary consequences.
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