On June 17, 2021, William Fischer et al., reported at medRxiv encouraging results with molnupiravir, the oral, direct-acting antiviral showing its effectiveness at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA.
In contrast to remdesivir, which is expensive, difficult to manufacture and must be given intravenously in a hospital, molnupiravir is an easier-to-synthesize, and oral direct-acting antiviral drug. These type of drugs function as “fake genetic building blocks that gum up the ability of viruses to copy their genomes faithfully”. Instead of inserting the correct RNA bases during replication, a viral enzyme called polymerase is tricked into incorporating derivatives of the drugs.
A study published in the Journal of Biological Chemistry indicates that the underlying mechanism of action by which the antiviral drug molnupiravir changes the viral genome is a process known as excessive mutagenesis or “error catastrophe.”
“The polymerase, or replication engine of the virus, mistakes molnupiravir molecules for the natural building blocks required for viral genome replication and mixes them in” explained Matthias Götte, the senior author of this study. “It causes the polymerase to make sloppy copies–nonsense genomes that are useless and not viable.”
The clinical trial of William Fischer et al., published in medRxiv, evaluated the safety and efficacy of the antiviral molnupiravir. In the study 204 participants were randomized and 202 received at least 1 dose of molnupiravir or placebo at 10 sites in the US. Eligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days.
Molnupiravir is taken in pill form every 12 hours for five days; a course consists of 10 pills.
This Phase 2a, randomized, double-blind clinical trial reports that molnupiravir expressed substantial antiviral efficacy, which included:
significantly reduced infectious virus isolation, time to elimination of SARS-CoV-2 RNA
increased proportion of participants that cleared SARS-CoV-2 RNA
and a greater reduction in SARS-CoV-2 viral RNA from baseline compared to placebo in outpatients with COVID-19.
Of note, four days after treatment initiation, there was no infectious virus isolated from any participants who received 400 or 800 mg molnupiravir.
Thus, it appears that molnupiravir is the first oral, direct-acting antiviral shown to be highly effective in reducing replication of SARS-CoV-2 and accelerating clearance of the infectious virus.