A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes.

A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes.

Publication date: Sep 25, 2023

Molnupiravir, an antiviral medication that has been widely used against SARS-CoV-2, acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus, and many will be lethal, and so molnupiravir-induced elevated mutation rates reduce viral load. However, if some patients treated with molnupiravir do not fully clear SARS-CoV-2 infections, there could be the potential for onward transmission of molnupiravir-mutated viruses. Here we show that SARS-CoV-2 sequencing databases contain extensive evidence of molnupiravir mutagenesis. Using a systematic approach, we find that a specific class of long phylogenetic branches, distinguished by a high proportion of G-to-A and C-to-T mutations, appear almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age-groups with widespread usage of the drug. We identify a mutational spectrum, with preferred nucleotide contexts, from viruses in patients known to have been treated with molnupiravir and show that its signature matches that seen in these long branches, in some cases with onwards transmission of molnupiravir-derived lineages. Finally, we analyse treatment records to confirm a direct association between these high G-to-A branches and the use of molnupiravir.

Concepts Keywords
Genomes Branches
Lethal Cov
Medication High
Viral Long
Molnupiravir
Mutational
Mutations
Sars
Signature
Transmission
Treated
Treatment
Virus
Viruses

Semantics

Type Source Name
disease IDO replication
disease MESH mutation rates
disease MESH SARS-CoV-2 infections
disease VO Viruses

Original Article

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