09-25-2023, 09:45 PM
Ugh. I hate when news headlines like this are so misleading... we need to do a deeper dive on the information presented. Here's the abstract for the study to which they are referring:
"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 load1,2. 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."
... so in other words, evolution gonna happen. No surprises there. If you treat an infection with a drug, you may end up selecting for resistant strains ... this has already been seen for decades with bacteria and such. Also that if you don't completely eliminate the infection, you might be more likely to see resistant strains survive. It is true that as a nucleoside prodrug, it might be more likely to cause mutations and therefore produce mutations and/or variants of concern, but I would think this would be true of most nucleoside analogs, and especially if the infection isn't actually eliminated by the drug. This might be a good argument to stick with protease inhibitors like Paxlovid.
"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 load1,2. 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."
... so in other words, evolution gonna happen. No surprises there. If you treat an infection with a drug, you may end up selecting for resistant strains ... this has already been seen for decades with bacteria and such. Also that if you don't completely eliminate the infection, you might be more likely to see resistant strains survive. It is true that as a nucleoside prodrug, it might be more likely to cause mutations and therefore produce mutations and/or variants of concern, but I would think this would be true of most nucleoside analogs, and especially if the infection isn't actually eliminated by the drug. This might be a good argument to stick with protease inhibitors like Paxlovid.