Molnupiravir antiviral, a major breakthrough in the treatment of COVID-19

The pharmaceutical company Merck recently announced that its antiviral drug molnupiravir is halving hospitalization and mortality for patients most at risk of developing severe forms of COVID-19.

• Also read: From immunization to intensive care

Although the accelerated development of vaccines against COVID-19 has made it possible to significantly reduce the number of people affected by this disease, the fact remains that the coronavirus continues to wreak havoc in some regions of the world.

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Whether the lack or even the lack of vaccines in certain countries, the reluctance of a section of the public to be vaccinated or the emergence of new, more infectious variants, all these factors hinder efforts to curb the minimization of the spread of the virus.

It should also not be forgotten that this virus is very likely to become endemic and therefore can evolve into more resistant forms of vaccines.

For all these reasons, the development of new therapeutic agents capable of neutralizing the virus, or at least reducing the severity of the infection, is of considerable importance.

A special antiviral

One antiviral drug that is generating a lot of interest is molnupiravir, a nucleoside analogue that targets RNA polymerase involved in genome copying and transcription of several viral genomes, including that of the SARS-CoV-2 coronavirus.

Unlike other antivirals, such as remdesivir (which ultimately proved ineffective in inhibiting the development of COVID-19), molnupiravir does not directly block polymerase activity. This molecule acts insidiously, allowing the enzyme to integrate it into the newly formed RNA strand: over time, the accumulation of molnupiravir in the viral RNA creates so many copying errors that reproduction can no longer continue and causes death of the virus. phenomenon called lethal mutagenesis (1).

Another extremely interesting point of molnupiravir is its effectiveness in the form of oral tablets, which significantly simplifies its administration to patients.

A turning point

Merck & Co. has just announced the results of a Phase III trial to determine the clinical potential of molnupiravir in patients with moderate to severe COVID-19 who have at least one risk factor for progressing to more severe stages of the disease.

The results are quite dramatic and probably represent a turning point in our fight against COVID-19: the study reports that there were 7.3% hospitalized in the group treated with a five-day molnupiravir cycle and no deaths, compared with 14.3% of hospitalizations in hospital and eight deaths in the placebo group.

Therefore, this is a 50% reduction in the risk of progressing to advanced stages of the disease, a protection that could not be observed for any of the medications tested so far.

Two other points worth noting:

  1. analysis of the viruses responsible for the various cases of COVID-19 in the study shows that the drug is effective against all circulating variants (including delta);
  2. the study was terminated prematurely for ethical reasons by the monitoring and follow-up committee (group of independent experts monitoring clinical trial data) due to the great superiority of treatment over placebo.

Therefore, these are truly extraordinary results that will lead to a request for authorization from the US Drug Enforcement Administration (FDA) for molnupiravir as an oral treatment against COVID-19.

Therefore, we will have two very effective vaccines to prevent COVID-19 and a very effective medicine to reduce the risk of complications and death in those who are infected. This is an incredible scientific achievement, achieved in just one year!

(1) Malone B and EA Campbell. Molnupiravir: coding for disaster. Nat. Structure. Mol. Biol. 2021; 28: 706-708.

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