Description
Prodrug of antiviral nucleoside analog; inhibits SARS-CoV, SARS-CoV-2 and MERS-CoV infection.
Definition
ChEBI: Molnupiravir is a nucleoside analogue that is N(4)-hydroxycytidine in which the 5'-hydroxy group is replaced by a (2-methylpropanoyl)oxy group. It is the prodrug of the active antiviral ribonucleoside analog N(4)-hydroxycytidine (EIDD-1931), has activity against a number of RNA viruses including SARS-CoV-2, MERS-CoV, and seasonal and pandemic influenza viruses. It is currently in phase III trials for the treatment of patients with COVID-19. It has a role as a prodrug, an anticoronaviral agent and an antiviral drug. It is a nucleoside analogue, an isopropyl ester and a ketoxime. It is functionally related to a N(4)-hydroxycytidine.
Biological Activity
Molnupiravir is a broad-spectrum antiviral prodrug of the nucleoside analog β-D-N4-hydroxycytidine (NHC). It competes predominantly with CTP for incorporation; it induces lethal viral mutagenesis by increasing G to A and C to U transition mutations without inhibition of RNA synthesis in replicating coronaviruses, which prevents the development of viral resistance. In primary airway epithelial cell cultures, Molnupiravir dose-dependently inhibits SARS-CoV-2 infectious virus production; it also inhibits MERS-CoV and SARS-CoV with EC50 values in the submicromolar range. In mice infected with SARS-CoV or MERS-CoV, it improves pulmonary function, and reduces virus titer and body weight loss. Molnupiravir also displays in vivo efficacy against seasonal and pandemic influenza A shed virus. It is orally bioavailable.
