Will anti-Covid-19 treatments create mutant viruses?

These last weeks, Pfizer and Merck have both announced the success of their anti-Covid pill trials. the molnupiravir of Merck was thus approved on November 5th by UK, after studies showing a 50% reduction the risk of hospitalization and death. Pfizer’s paxlovid pill would be 89% effective to prevent the risk of hospitalization and death. Molnupiravir works against virus by creating multiple errors in its DNA, which is believed to result in a non-functioning virus. But for William Haseltin, a virologist at Harvard University known in particular for his research on the AIDS virus, this drug could induce dangerous mutations and thus make the bed of new more resistant variants. ” Molnupiravir has the mutagenic potential to alter the functions of the virus, but not to prevent it from replicating and giving rise to a future dominant variant “, warns the specialist, who nevertheless claims to be a fervent supporter of antivirals.

The researcher cites a series of experiments showing that coronaviruses like MERS-CoV can develop a resistance against molnupiravir, somewhat on the principle of antibiotic resistant bacteria. During the experiment, more than 41 mutations of the virus were detected after the treatment in different places of the genome. Even more worrying: the more you increase the amount of molnupiravir, the more it generates mutations, in particular on the protein state-of-the-art, the one targeted by vaccines. ” This shows that the virus survives and continues to grow despite the large number of mutations it undergoes. William Haseltin warns. The virus replicates a little slower, but if we administer molnupiravir on a large scale, this slight disadvantage will disappear and we will have a perfectly favorable environment for the virus.emergence of a new dangerous variant, continues the researcher.

Theoretically, the dose of molnupiravir (800 mg per pill) is sufficient to induce enough mutations that will kill the virus. ” The problem is, in reality, people are not taking their treatment correctly. “, Argues the scientist. For the antibiotics for example, only 40% of patients complete their treatment, which produces bacteria long-term resistant. In a second article, William Haseltin warns of another possible deleterious effect of molnupiravir, which may be capable of inducing tumors and miscarriages, by introducing mutations into the genome of the recipient. This mutagenic potential has been verified by laboratories, but not seriously enough, judges the virologist.

Reservoirs for new variants

Are all these fears justified? The magazine Science asked the question to several specialists, who downplay the words of William Haseltin. ” When you force the virus to mutate, it will certainly be able to become resistant but will above all develop deleterious mutations. », Judge Mark Denison, virologist at Vanderbilt University (United States). The main risk of seeing variants appear in people who are immunocompromised, in whom the virus can remain in the body for several months. In June, doctors reported the case of a patient in whom the virus had remained six months while continuing to accumulate mutations, some of which induce resistance to antibody. However, immunocompromised patients are precisely one of the main targets of molnupiravir, which must prevent this phenomenon.

On the side of Merck, it is ensured that no mutant virus was detected in the patients who followed the treatment. Another possibility to prevent the risk of new variants would be to administer a combination of the pills from Merck and Pfizer, which work a little different, suggests Science. A bit like the triple therapies versus AIDS, which target different mechanisms of the virus.