- Guide to PHARMACOLOGY
Synonyms: EIDD-2801 | EIDD2801 | Lagevrio® | MK-4482 | MK4482
molnupiravir is an approved drug (UK (2021))
Compound class: Synthetic organic
Comment: Molnupiravir (EIDD-2801, MK-4482) is an oral, broad-spectrum antiviral drug [1,8]. The proposed INN molnupiravir was released by the WHO in a special release to cover COVID-related therapeutics in October 2020 (Proposed INN: List 124-COVID-19). Chemically molnupiravir is the isopropylester prodrug of the ribonucleoside analogue β-D-N4-hydroxycytidine (EIDD-1931, or N-hydroxycytidine) [10-11]. Functionally, the active form of molnupiravir is incorporated into the virus' RNA by the viral RNA-dependent RNA polymerase (RdRp) during replication, which results in lethal mutagenesis . Molnupiravir was originally designed by Emory University scientists to inhibit replication of influenza virus. It has subsequently been tested for activity against other RNA viruses, including pandemic SARS-CoV-2, SARS-CoV and MERS-CoV . Molnupiravir was being progressed for COVID-19 in a collaboration between Ridgeback Biotherapeutics and Merck. In vivo therapeutic and prophylactic potential was reported in a peer reviewed manuscript in February 2021 .
There is concern that molnupiravir may induce mutations in the host, based on evidence from mammalian cell culture experiments  and using the Ames test (bacteria).
|The active form of EIDD-2801 exists in two tautomeric states, one which is a uridine mimic (pairs with adenosine), and the second which mimics cytidine (pairs with guanosine) . During RNA replication switching between these tautomers causes mismatches and leads to catastrophic mutation within the new viral RNA transcripts which render it non-functional. Remdesivir is another nucleoside analogue that is being evaluated in human trials for efficacy against SARS-CoV-2 infection. The active forms of both compounds block viral RNA-dependent RNA polymerase to prevent virus replication, but in slightly different ways, suggesting that their effects may be complementary. Another difference between remdesivir and EIDD-2801 is that while remdesivir needs to be administered intravenously within a medical setting, EIDD-2801 is orally bioavailable, so could be taken at home. This offers the potential for treatment to be initiated earlier in the course of the disease, before more severe symptoms develop.|