Antiviral drug molnupiravir is associated with new mutations in SARS-CoV-2

New evidence suggests that the antiviral drug molnupiravir, used to treat patients with COVID-19, appears to be causing SARS-CoV-2 to mutate and evolve, and that some of these new viruses are becoming more transmissible. This was shown in a study. But it's unclear whether these mutated viruses pose an increased risk to patients or whether they can evade vaccines.

The drug works by disrupting the genome of the virus, causing random mutations as it replicates, weakening the virus and preventing it from replicating, thereby allowing it to eliminate infection.

However, in a study published today in Nature, scientists show that in some cases, patients treated with molnupiravir can transmit variants of the virus and spread them in the community. Ta.

Molnupiravir is one of many drugs being used to fight COVID-19. It belongs to a class of drugs that can mutate the virus to the point where it becomes fatally weakened. However, it has been found that in some patients, this process does not kill all the virus and may allow some mutated viruses to spread. This is important to consider when evaluating the overall benefits and risks of molnupiravir and similar drugs. ”

Dr Christopher Lewis, University of Cambridge Medical School

Molnupiravir, sold under the brand name Radebrio, is approved to treat COVID-19 in several countries, including the UK, US and Japan. It has been used to treat this disease since late 2021.

Molnupiravir is converted in the body into a molecule that disrupts the genome of the SARS-CoV-2 virus, introducing several nucleotide mutations into the RNA, randomly changing some C's to T's and some G's to As's. . These changes mean that as the virus replicates, the progeny become weaker, the rate at which the virus replicates decreases, and the virus is cleared from the body.

However, there are concerns that in some cases, many mutated viruses may not be killed off quickly enough and may therefore be able to infect others, allowing new mutated viruses to spread. has been expressed.

During the COVID-19 pandemic, many countries, led by the Cambridge-led COVID-19 Genomics UK Consortium, sequenced virus samples and shared the information with the Global Initiative for Sharing All Influenza Data (GISAID). and the International Influenza Data Sharing Initiative. Nucleotide Sequence Database Collaboration (INSDC). This allows scientists and public health agencies to track the evolution and spread of the virus, especially those with so-called “variants of concern,” meaning those that are more transmissible, more deadly, or more transmissible. It is now possible to pay attention to versions of the virus with possible mutations. Some types, such as the delta and omicron types, can evade a vaccinated person's immune system.

A team of researchers from the UK and South Africa noticed a large number of viral genomes containing a number of mutations, particularly those that changed C to T and G to As. While C to T mutations are relatively common overall in the evolution of SARS-CoV-2, G to A mutations are much less frequent, and a higher proportion of G to A mutations are associated with molnupiravir. related to treatment.

The team then analyzed the family tree of more than 15 million SARS-CoV-2 sequences in the GISAID and INSDC databases to see what mutations occurred at each point in the virus's evolutionary history. They found that viruses with characteristics of this mutation began to appear starting in 2022, almost exclusively in countries and age groups where molnupiravir was widely used to treat COVID-19 infections.

To confirm this link, researchers looked at treatment records in the UK and found that at least one in three cases of the virus that showed mutated features involved the use of molnupiravir.

Researchers have also identified small clusters of patients infected with the mutated viruses, suggesting that these new viruses were being transmitted from person to person. However, so far, none of the known variants of concern have been linked to the use of molnupiravir.

Dr Theo Sanderson from the Francis Crick Institute said: 'COVID-19 continues to have a major impact on human health, and some people find it difficult to clear the virus. It is important to develop drugs for this purpose.” However, our evidence shows that the specific antiviral drug molnupiravir also induces new mutations and increases the genetic diversity of the surviving viral population.

“Our findings will help in the ongoing evaluation of the risks and benefits of molnupiravir treatment. The potential for persistent antiviral drug-induced mutations must be considered for the development of new drugs that act similarly. there is.”

This research was funded by Wellcome, Cancer Research UK, Medical Research Council, National Institute for Health and Care Research, Fondation Botnar, UK Cystic Fibrosis Trust and Oxford Martin School.