It is the second oral medication against COVID 19 after nirmatrelvir/ritonavir, but with a lower efficacy: about 30% (95% CI, 1–51%) against hospitalization or death in unvaccinated adults with mild or moderate COVID-19 and at least one risk factor for disease progression. Contraindications
Use during pregnancy is not recommended. There are no human data on use during pregnancy to assess the risk of adverse maternal or fetal outcomes. Based on animal data, the drug may cause fetal harm.In rats, bone and cartilage toxicity was observed after repeated dosing. Adverse effects
Adverse reactions observed in the phase III MOVe-OUT study included diarrhea (2%), nausea (1%) and dizziness (1%), all of which were mild or moderate. Overdose
The effects of overdose are unknown, treatment consists of general supportive measures such as monitoring of clinical status. Drug interactions
Based on limited available data, there are no drug interactions. Mechanism of action
Molnupiravir inhibits viral reproduction by promoting widespread mutations in the replication of viral RNA by RNA-directed RNA polymerase. It is metabolized into a ribonucleoside analog that resembles cytidine, β-D-N4-Hydroxycytidine 5′-triphosphate (also called EIDD-1931 5′-triphosphate or NHC-TP). During replication, the viruss enzyme incorporates NHC-TP into newly made RNA instead of using real cytidine. Molnupiravir can swap between two forms (tautomers), one of which mimics cytidine (C) and the other uridine (U). NHC-TP is not recognized as an error by the viruss proofreading exonuclease enzymes, which can replace mutated nucleotides with corrected versions. When the viral RNA polymerase attempts to copy RNA containing molnupiravir, it sometimes interprets it as C and sometimes as U.
This causes more mutations in all downstream copies than the virus can survive, an effect called viral error catastrophe or lethal mutagenesis. Chemistry
The first synthesis of molnupiravir was disclosed in a patent filed by Emory University in 2018.In the first step, acetone is used as a protecting group to render two of the three hydroxy groups of uridine unreactive to treatment with the acid anhydride of isobutyric acid, which converts the third hydroxy group to its ester. Treatment with 1,2,4-triazole and phosphoryl chloride produces a reactive intermediate in which the triazole portion can be replaced with hydroxylamine. Finally, removal of the protecting group using formic acid converts the material to molnupiravir. : 93–95 
Alternative patented routes to molnupiravir have been reviewed. History
Molnupiravir was developed at Emory University by its drug innovation company, Drug Innovation Ventures at Emory (DRIVE). In 2014, DRIVE began a screening project funded by the Defense Threat Reduction Agency to find an antiviral drug targeting Venezuelan equine encephalitis virus (VEEV), which led to the discovery of EIDD-1931. When turned into the prodrug EIDD-2801 (molnupiravir), the compound also showed activity against other RNA viruses including influenza, Ebola, chikungunya, and various coronaviruses.The international nonproprietary name of the drug was inspired by that of Thors hammer, Mjölnir.