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One of the most common antiviral treatments used to treat Covid-19 appears to drive the virus to mutate and evolve.
Researchers at the University of Cambridge have found that the drug molnupiravir may, in some cases, be causing a mutated form of Covid-19 to transmit and spread through the community.
The findings, published in Nature, show the importance of assessing the benefits and risks of all Covid-19 treatments.
Molnupiravir is licensed in several countries, including the UK, USA and Japan, with the brand name Lagevrio, and has been used to treat Covid infections since 2021. It works by weakening the Covid virus. Once inside the body, the medication is converted into a molecule that introduces nucleotides into the RNA and changes the DNA bases from Cs to Ts and Gs to As. This mutation fatally weakens the virus’s ability to replicate itself and disrupts the spread of Covid-19 throughout the body. In some cases, the weakened virus is not being killed off quickly enough by the body and is transmitted through the community.
Dr Christopher Ruis from the Department of Medicine at the University of Cambridge said: ‘Molnupiravir is one of a number of drugs being used to fight Covid-19. But what we’ve found is that in some patients, this process doesn’t kill all the viruses, and some mutated viruses can spread. This is important to take into account when assessing the overall benefits and risks of molnupiravir and similar drugs.’
During the pandemic, the virus was being sequenced by the Cambridge-led Covid-19 Geonomics UK Consortium to track the evolution of the virus. The information was compiled into the Global Initiative on Sharing All Influenza Data (GISAID) and the International Nucleotide Sequence Database Collaboration (INSDC) and used by scientists and public health agencies around the world to monitor ‘variants of concern’. This includes variants that are more transmittable and more lethal, as well as mutations that evade vaccinated people’s immune systems, such as the Delta and Omicron variants.
Teams of scientists from the UK and South Africa, who were examining the genome data, began to notice an increase in the number of mutations of the SARS-CoV-2 sequences virus, particularly mutations associated with changing Gs to As, which had previously been a less common mutation.
Researchers at the University of Cambridge began an examination of the ‘family tree’ of 15 million SARS-CoV-2 sequences from the GISAID and INSDC databases. They found that the viruses with a mutation that involved changing Gs to As emerged from 2022 onwards in countries and age groups where molnupiravir was widely used for antiviral treatment.
To confirm the link, the researchers examined Covid-19 treatment records in England and found that at least one in three infections showing this mutation involved the use of molnupiravir. Clusters of infections by the mutated virus were also apparent in the data, indicating the new form of the virus was passed on from person to person. However, none of the variants of concern so far have been linked to the use of molnupiravir.
Dr Theo Sanderson from the Francis Crick Institute said: ‘Covid-19 is still having a major effect on human health, and some people have difficulty clearing the virus, so it’s important we develop drugs which aim to cut short the length of infection. The possibility of persistent antiviral-induced mutations needs to be taken into account for the development of new drugs.’
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