"Molnupiravir treatment has left a visible trace in global sequencing databases" of the genome of the virus, concludes a study published Monday in the journal Nature.

Molnupiravir is a treatment developed by the American pharmaceutical giant Merck (known as MSD internationally).

Launched in 2021, it was the first anti-Covid pill, a significant step forward for a pharmaceutical arsenal that until then consisted only of vaccines and treatments requiring complex intravenous administration.

But molnupiravir, sold under the name Lagevrio, soon came under criticism. These were partly aimed at its limited effectiveness, especially compared to its great competitor, Pfizer's Paxlovid, which quickly joined it in the market.

Above all, its mode of action has provoked strong reluctance. Unlike other antivirals, such as Paxlovid, Lagevrio works by integrating directly into the genome of the virus.

The goal is to trigger a series of increasingly disordered mutations that eventually lead to the extinction of the virus in the body. But researchers have, since its launch, estimated that this mechanism could promote the appearance of mutant and transmissible viruses from one individual to another.

Specific "signature"

This risk had contributed to a certain reluctance of health authorities such as the American FDA, which had approved molnupiravir only by a small majority, or the French High Authority of Health (HAS), which rejected it altogether.

It is in this context that the study published on Monday is inscribed, while the star of the Merck pill has already faded in view of its low effectiveness but it is still widely prescribed in some countries, especially in the developing world.

The researchers studied a large database, called Gisaid, which gathers the genomes of viruses collected from many patients around the world.

For them, the conclusion is clear: the use of molnupiravir is associated with the appearance of specific mutations.

They found the appearance of a specific "signature" at the time when the pill had begun to be prescribed in some countries. In contrast, it is almost absent from places where treatment was not approved.

In summary, this treatment "can give rise to viruses that have mutated significantly and remain viable, or even in some cases transmissible," explained to AFP one of the authors, geneticist Theo Sanderson.

These conclusions were rejected by Merck. According to the American laboratory, the study only highlights a correlation without making it possible to affirm a causal link between its treatment and these mutations.

The authors rely on "circumstantial associations", the group told AFP.

No immediate risk

Still, the study convinces several researchers who did not participate, such as virologist Stephen Griffin who praised the British Science Media Center (SMC) for a work "well done and of exceptional importance".

Like the authors of the study, he insists on one point: the mutations identified do not seem, in themselves, to have been particularly dangerous or contagious.

"But these findings have important implications for the future of the pandemic," Griffin warns.

Indeed, any phenomenon that accelerates the mutations of the virus runs the risk of giving rise to variants that are more dangerous or, as Omicron was when it appeared, are much more transmissible than its predecessors.

In this context, should we stop prescribing molnupiravir? The authors of the study are careful not to comment, remaining in the field of genetics and referring the health authorities to their responsibilities.

And for some researchers, if these results remind us of the need not to prescribe molnupiravir at arm's length, it should not be given up altogether.

"Of course, you should not systematically take molnupiravir when you are infected" with the coronavirus, concludes infectious disease specialist Chris Butler with the SMC. "But in some difficult cases, it's a drug that can be very helpful."

© 2023 AFP