Molnupiravir (MOV, MK-4482, EIDD-2801), an orally administered prodrug of N-hydroxycytidine (NHC, EIDD-1931), has broad antiviral activity against a spectrum of RNA viruses. MOV causes viral error catastrophe after infiltrating the viral genome.

Due to the unique mechanism of action of MOV, its activity remains affected by changes in the spike protein seen in SARS-CoV-2 variants of concern. A study investigated the activity of MOV against variants by evaluating antiviral activity in an in vitro infection assay and virologic response for treating COVID-19.

It was observed that-

• NHC was equally effective against SARS-CoV-2 variants B.1.1.7 (20I), B.1351 (20H), and P1 (20J), compared with the original WA1 (19B) isolate in-vitro.
• No discernable difference was present in the magnitude of viral response measured by change from baseline in RNA titer over time across all clades represented including 20A through 20E and 20G to 20I, in clinical trials.
• No enrolled subject was presented with 20F, 20J, or 21A.

Thus it was concluded that the distribution of clades in participants in MOVe-In and MOVe-Out was representative of those circulating globally at the time of collection. Thus the undisturbed antiviral activity of MOV despite spike protein substitutions, proved by both in vitro and clinical trials, suggests its potential use for the treatment of SARS-CoV-2 variants.

Source- Open Forum Infectious Diseases, 2021;8(1):S373. https://doi.org/10.1093/ofid/ofab466.742