The exploration for effective drugs to treat COVID-19 is the need of time. The clinical application of remdesivir is limited due to its intravenous administration, unstable concentrations in plasma and variable antiviral activity in different organelles.

Four neutralising antibodies (bamlanivimab, etesevimab, casirivimab, and imdevimab) have also been approved by the United States Food and Drug Administration; but their high cost and need for intravenous administration limits their use. Thus, effective and economical oral drugs are needed to prevent and control COVID-19, as they can be administered after exposure to SARS-CoV-2 or at the first sign of COVID-19.

Molnupiravir is an oral antiviral drug with β-d-N-hydroxycytidine (NHC) as the active ingredient, which can pair with adenine or guanine to generate lethal mutations during subsequent RNA synthesis. NHC does not conclude strand synthesis and is therefore resistant to the proofreading function of SARS-CoV-2 nsp14.

Phase 3 MOVe-OUT trial has demonstrated that treatment with molnupiravir can reduce hospitalisation or mortality by approximately 50% compared with placebo in patients with mild or moderate COVID-19. Molnupiravir proved superior to remdesivir (with 50% inhibitory concentration [IC50]: 0·3 μmol/L vs 0·77 μmol/L) and ideal toxicity (50% cytotoxic concentration [CC50]>10 μmol/L) in vitro.

It also proved promising in phase 2 clinical trial as no live viruses were isolated from patients who received 400 mg or 800 mg molnupiravir for 5 days, contrasting 11·1% of patients in the placebo group. Additionally, molnupiravir shows a favourable safety and tolerability profile. However, 7·3% of participants treated with molnupiravir were still hospitalised during a 29-day observation period and the potential for molnupiravir to be carcinogenic needs further study. 

Since COVID-19 is prevailing, the combined use of immunomodulatory or anti-inflammatory agents, antivirals, and host-factor antagonists might prove beneficial for treating the disease. The Discovery of affordable and powerful oral anti-COVID-19 drugs and the increased vaccination rate will bring hope for the end of the COVID-19 pandemic.

SOURCE- The Lancet, Microbe, 2022;3(2). DOI:https://doi.org/10.1016/S2666-5247(21)00278-0