RESUMEN
Molnupiravir, an antiviral medication widely used against severe acute respiratory syndrome coronavirus 2 (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; thus, molnupiravir-induced elevated mutation rates reduce viral load1,2. However, if some patients treated with molnupiravir do not fully clear the 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, are found almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age groups with widespread use 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 onward 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.
Asunto(s)
Antivirales , COVID-19 , Citidina , Hidroxilaminas , Mutagénesis , Mutación , SARS-CoV-2 , Humanos , Antivirales/farmacología , Antivirales/uso terapéutico , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/virología , Citidina/análogos & derivados , Citidina/farmacología , Citidina/uso terapéutico , Genoma Viral/efectos de los fármacos , Genoma Viral/genética , Hidroxilaminas/farmacología , Hidroxilaminas/uso terapéutico , Mutación/efectos de los fármacos , Filogenia , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/genética , Carga Viral , Replicación Viral/efectos de los fármacos , Replicación Viral/genética , Evolución Molecular , Mutagénesis/efectos de los fármacos , Tratamiento Farmacológico de COVID-19RESUMEN
Since SARS-CoV-2 BA.5 (Omicron) emerged and spread in 2022, Omicron lineages have markedly diversified. Here we review the evolutionary trajectories and processes that underpin the emergence of these lineages, and identify the most prevalent sublineages. We discuss the potential origins of second-generation BA.2 lineages. Simple and complex recombination, antigenic drift and convergent evolution have enabled SARS-CoV-2 to accumulate mutations that alter its antigenicity. We also discuss the potential evolutionary trajectories of SARS-CoV-2 in the future.