Study Says Merck’s COVID Drug Linked to Spreading Mutants

Posted on 02/02/2023

Molnupiravir is sold under the brand name Lagevrio. The drug is an is an antiviral medication that seeks to inhibt the replication of certain RNA viruses. Molnupiravir is produced by Merck & Co., a competitor to Pfizer Inc. Molnupiravir is designed to kill the virus by inducing mutations in the viral genome. In late 2021, the drug was authorized for use in the United Kingdom and the United States. Molnupiravir was the first oral antiviral approved anywhere to combat COVID-19. The drug has since been authorized in dozens of other countries.

In 2022, Merck estimated global sales of the drug at more than US$ 5 billion. Viable mutations of the coronavirus can survive the molnupiravir treatments and end up competing against existing COVID variants. Merck disputes the view that its drug is causing problematic COVID variants.

In a report by medRxiv, called “Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases” there is a possibility that the drug could prolong and even reinvigorate the pandemic. Researchers are worried that the drug could catalyze more contagious or health-threatening variations of COVID.

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. Molnupiravir-induced elevated mutation rates have been shown to decrease viral load in animal models. However, it is possible that some patients treated with molnupiravir might not fully clear SARS-CoV-2 infections, with the potential for onward transmission of molnupiravir-mutated viruses. We set out to systematically investigate global sequencing databases for a signature of molnupiravir mutagenesis. We find that a specific class of long phylogenetic branches 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 calculate a mutational spectrum from the AGILE placebo-controlled clinical trial of molnupiravir and show that its signature, with elevated G-to-A and C-to-T rates, largely corresponds to the mutational spectrum seen in these long branches. Our data suggest a signature of molnupiravir mutagenesis can be seen in global sequencing databases, in some cases with onwards transmission.

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