A new antiviral drug molnupiravir has garnered much attention recently as the first oral antiviral drug for Covid-19. It has been developed by Merck in collaboration with Ridgeback therapeutics.

Molnupiravir was first developed as a possible treatment of influenza viruses and has earlier been shown to have some activity against viruses that use RNA-dependent RNA polymerase (RdRp) for replication. It is the orally bioavailable 5′-isobutyrate prodrug of a direct-acting antiviral ribonucleoside analog, β-D-N4-hydroxycytidine, or EIDD-1931. In the plasma the drug is cleaved by host esterases to its active form EIDD-1931 or b-D-N4-hydroxycytidine (NHC), which is then phosphorylated intracellularly to its corresponding 5′-triphosphate in the tissues. These two steps of its mechanism of action contribute to the broad-spectrum antiviral activity of molnupiravir. ^1.2

Preclinical trials have demonstrated the activity of molnupiravir against SARS-CoV-2 including the most common SARS-CoV-2 variants. Its safety and tolerability against SARS-CoV-2 has been demonstrated in phase 1, 2 and 3 trials. Interim results from the Phase 3 MOVe-OUT trial have shown that molnupiravir, when administered ≤5 days of onset of symptoms, reduced the risk of hospitalization or death by nearly 50% in at risk, non-hospitalized adults with mild to moderate Covid-19. However, its effectiveness in moderate to severe illness is yet to be established.

The fact that it can be taken orally as outpatients and requires to be administered only for five days will surely result in better patient compliance to treatment. Moreover, it does not require cold storage.

Britain has become the first country to approve use of molnupiravir after the drug was given the green signal by its Medicines and Healthcare products Regulatory Agency (MHRA) on Thursday. It is recommended for use “as soon as possible following a positive COVID-19 test and within five days of symptoms onset”. It is approved for use in patients with mild to moderate Covid-19 and at least one risk factor such as obesity, older age (>60 years), diabetes mellitus, or heart disease, which puts them at risk of developing severe disease.³ However, molnupiravir is yet to be approved in the United States.

Will it prove to be the game changer in the battle against Covid-19? Only time will tell.

References

1. Singh AK, et al. Molnupiravir in COVID-19: A systematic review of literature. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2021;15: 102329.
2. Holman W, et al. Accelerated first-in-human clinical trial of EIDD-2801/MK-4482 (molnupiravir), a ribonucleoside analog with potent antiviral activity against SARS-CoV-2. Trials. 2021 Aug 23;22(1):561.
3. MHRA. https://www.gov.uk/government/news/first-oral-antiviral-for-covid-19-lagevrio-molnupiravir-approved-by-mhra. 4 November 2021.