Research results have shown that ‘Lagebrio’ (photo, ingredient molnupiravir), an oral treatment for COVID-19, can cause mutations in the COVID-19 virus itself, and that this mutation can spread to other people./News 1
Research results have shown that ‘Lagevrio (ingredient molnupiravir)’, an oral treatment for novel coronavirus infection (COVID-19) developed by Merck & Co. (MSD) of the United States, can cause mutations, and that these mutations can spread to other people. There has been controversy in the past that Laguebrio causes COVID-19 mutations, but one more scientific basis has been added to support this.
Theo Sanderson, a research team at the Francis Crick Institute in the UK, announced on the 25th that they had discovered a mutation pattern that appears to have been induced by Laguebrio as a result of analyzing a database of over 15 million COVID-19 virus sequences collected from around the world by the International Organization for Sharing Influenza Information (GISAID). . The probability of this mutation occurring in people who took Lagebrio was found to be eight times greater than in people who did not take it.
LaGevrio is a COVID-19 treatment developed by Merck, and its main ingredient is molnupiravir. This is the principle of interfering with the viral genome (RNA) while the COVID-19 virus is multiplying in human cells. For this reason, from the beginning of development, there were concerns that Lagebrio might affect human DNA, causing cancer or deformities.
The frequency of COVID-19 mutation occurrence (left) shown in the global COVID-19 sequencing database and the frequency of COVID-19 mutation occurrence (right) in the patient group taking Lagevrio (ingredient molnupiravir) were similar./Theo Sanderson, Nature (2023)
Molnupiravir can sneak into the cytosine (C) position among the bases that make up the COVID-19 virus genome. This is because the molecular structure is similar to cytosine. And here, it mimics thymine (T) or uracil (U), which are bases with similar structures. It can also be inserted into the place of guanine (G), pretending to be adenine (A). Ultimately, it prevents the virus from multiplying normally and eliminates it.
The researchers analyzed that the number of COVID-19 viruses with this mutation pattern has increased around the world since 2022, when LaGevrio was introduced. When compared to the COVID-19 virus from the patient group that took LaGevrio, the mutation pattern was similar.
In particular, many of these mutations were confirmed in countries that had used Lagebrio since that year, such as the UK, Australia, the US, and Japan, especially in the elderly. The researchers analyzed that this may be because in countries that have approved both Paxvride and Lagevrio, Lagevrio is more often prescribed to the elderly than Paxvride, which has many contraindicated drugs. On the other hand, such mutations were less common in countries that did not approve LaGevrio, such as Canada and France.
Of course, viruses always mutate and evolve. This is to trick the immune system into infecting more hosts and multiplying. Additionally, the COVID-19 virus naturally changes C to U relatively frequently. However, when taking Lagebrio, the frequency of these mutations increased by about six times. Mutations from G to A, U to C, and A to G, which rarely occur in nature, also increased by about 5 to 20 times.
Researcher Sanderson explained, “Molnupiravir causes new mutations, allowing viruses that survive drug treatment to have genetic diversity,” and added, “The results of this study should be taken into consideration when developing antiviral drugs that act in a similar way.”
The researchers stated that it is not yet known whether molnupiravir created new mutations in COVID-19 or had any effect on the route and speed of the virus’ spread.
The research team previously published research results showing that molnupiravir causes mutations in the COVID-19 virus in January and August on ‘medRxiv,’ a site for publishing advance papers in the medical field. This time, using a larger database than at the time, they announced the results of analyzing how many of each mutation would occur when taking Lagebrio.
Experts still offer mixed opinions on this. Cho Nae-sun Lee, director of the Virology Research Center at Harvard University Medical School, said, “There is fundamental concern because of the principle of action of preventing viruses by causing mutations.” On the other hand, Jesse Bloom, a professor at the Fred Hutchinson Cancer Research Center in the U.S., said, “Coronaviruses naturally mutate frequently,” and added, “There is a need to conduct additional research to determine how much antiviral drugs will affect the evolution of the virus.”
The results of this study were published in the international academic journal ‘Nature’ on the 25th.
Nature(2023) DOI: 10.1038/s41586-023-06649-6
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