Antiviral Molnupiravir release to Covid-19 raises concern about cancer and mutations

Segundo o laboratório, os resultados da análise interina do estudo de fase 3 mostraram que o Molnupiravir reduziu significativamente o risco de hospitalização ou morte pela Covid-19.
According to the laboratory, the results of the interim analysis of the phase 3 study showed that Molnupiravir significantly reduced the risk of hospitalization or death from Covid -10.| Photo: EFE

The antiviral Molnupirvir, by Merck pharmaceutical, was approved for emergency use against Covid-10 in the US and India. With no double-blind randomized trials yet, Merck reported that its drug reduces the chance of hospitalization with the disease by about 30% — some Brazilian patients were included in the pilot study.

Fluvoxamine, a cheap antidepressant that has been shown to be effective in resubmission as Covid’s early treatment, has equal or greater efficacy than that reported by Merck, with the advantage that it has two double-blind studies in its favor. There is another advantage: unlike Molnupiravir, it is not an agent that causes mutations in the virus.

It seems strange, for some specialists, that a drug that could lead to new variants is proposed as a treatment. This is the opinion of Michael Lin, a Stanford professor of neurobiology and bioengineering who works on the genetic engineering of viruses. “Would you rather (1) go back to normal activities sometime, or (2) we continually make new coronaviruses that escape vaccines and wear masks forever?” Lin said on Twitter. “If you chose 1, know this: Molnupiravir from Merck must not be approved.”

The reason for concern by Lin and others is the mechanism of action of Molnupiravir. It mimics one of the building blocks of the virus’s genetic material. So when the virus tries to replicate, it mutates. In the laboratory, the effect of this is to inactivate the virus, as most mutations are bad for it. However, in human organisms, considering the inevitable variation in the presence of the drug in the organism, mutations that favor viral replication could be maintained — it is Darwin’s process of natural selection that leads to adaptation.15172212Molnupiravir and the omicron variant

William Haseltine, professor of medicine at Harvard for nearly two decades and president of the health NGO ACCESS, raised hypotheses for the emergence of the variant omicron in Forbes magazine: it may have come from an immunocompromised patient where the virus has more opportunity to diversify, it may have jumped from humans to other animals and back to humans (we know that the SARS-CoV-2 virus is capable of infecting deer , dogs, cats and other animals), or may have come from a patient treated with Molnupiravir who did not take the full dose.

In the Merck study patients who took the drug, a greater viral variation was noticed, including 30 mutations in protein S, which the virus uses to enter our cells . The omicron variant has 30 mutations in this protein. The evidence is little better than merely pointing out that the drug is mutagenic, however. Merck had been using four locations in South Africa in its study since October, just before the omicron variant emerged in the region (in Botswana). In addition to the ideal dose to disable the virus, smaller doses were also tested.

15172212Finally, there is a molecular clue: the genetic material of the virus is like a long text composed of four “letters” that are smaller molecules: A, C, G and U. One type of mutation is changing one of these letters for another – we call it of point mutation. Molnupiravir does not cause point mutations with equal frequency: there is a preponderance of C → U and G → A. Comparing the genetic material of the omicron variant with the original Wuhan variant, it is observed that most of the point mutations are of this type preferred by the drug. When it is applied to other coronaviruses, this is the pattern observed, explains Haseltine. He himself makes it clear that this is a hypothesis, not something confirmed.

15172212 Haseltine also suspects that Molnupirvir could cause cancer in humans. Although the drug has already been tested on humans, samples from a few thousand people, as was the case, are usually not enough to capture rare but dangerous effects, which multiply into thousands of victims with the drug on the market. Notably, study participants were recommended to use contraceptives and abstain from sex while taking the drug.

Emergency use1517221215172212 The US Food and Drug Administration (FDA) states in its emergency use authorization for Molnupiravir that it is not approved for minors 10 years, for preventive use, and for use longer than five days. The authorization makes it clear that emergency use is for early treatment, not for hospitalized patients.

On its website, the manufacturer Merck celebrates the good results of using the drug in the pilot study: 1.433 patients were divided between those who received placebo and those who received Molnupirvir. While nine people died in the placebo group, only one died in the treatment group. Along with its partner Ridgeback Biotherapeutics, the pharmacist says the drug is being proposed for those people in whom the Covid picture-19 is still mild, but they are at risk of evolving to hospitalization and other more serious outcomes.

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