The Covid-19 pandemic has caused substantial global morbidity and mortality, and disruption of the economies. Some catastrophes among these could have been prevented with the development of deliverable, orally bioavailable, direct-acting antiviral therapeutics. 

Molnupiravir, the orally bioavailable prodrug of N4-hydroxycytidine (NHC), has shown some ray of hope. Formulated at the Emory Institute for Drug Development (EIDD), molnupiravir works effectively against influenza and many other RNA viruses, like SARS-CoV-2. 

NHC, on entering the cells, gets phosphorylated into its triphosphate derivative, which combines with viral RNA causing fatal errors in replication. Furthermore, it also has a high genetic barrier to resistance. Molnupiravir is found to be active against the three predominant circulating variants (delta, gamma, and mu), rendering a modest antiviral effect. 

Molnupiravir seems to be less beneficial when administered late in the disease course i.e. symptoms for more than 3 to 5 days or after hospitalization. It will also require careful monitoring for the emergence of any side effects. 

Since the drug has shown mutagenic effects in Chinese hamster ovary cells, potential mutagenic toxicity has been a concern. However, the potential mutagenicity and genotoxicity of molnupiravir have been explained by the accumulated data. Studying these data, regulatory authorities in the United Kingdom commented that there is less risk of mutagenicity or genotoxicity in the clinical use of molnupiravir, and is thus licensed for use in the United Kingdom.

Drug patents will probably be made open to the World Health Organization patent pool and manufacturers of generic drugs, to boost up the production of molnupiravir for developing countries, at a low cost.

Vaccines still enjoy the role of being the primary tool for protection against SARS-CoV-2; however, orally bioavailable medications will mark their importance in the management of this devastating disease. 

Source- The New England Journal of Medicine, December 16, 2021. DOI: 10.1056/NEJMe2117814