Molnupiravir

Molnupiravir (EIDD-2801, MK-4482) is the isopropylester prodrug of N4-hydroxycytidine. With improved oral bioavailability in non-human primates, it is hydrolyzed in vivo, and distributes into tissues where it becomes the active 5’-triphosphate form. The active drug incorporates into the genome of RNA viruses, leading to an accumulation of mutations known as viral error catastrophe. Recent studies have shown molnupiravir inhibits replication of human and bat coronaviruses, including SARS-CoV-2, in mice and human airway epithelial cells. A remdesivir resistant mutant mouse hepatitis virus has also been shown to have increased sensitivity to N4-hydroxycytidine.

Molnupiravir was granted approval by the UK's Medicines and Health products Regulatory Agency (MHRA) on 4 November 2021 to prevent severe outcomes such as hospitalization and death due to COVID-19 in adults. Molnupiravir was also granted emergency use authorization by the FDA on December 23, 2021; however, it is not yet fully approved.

N4-hydroxycytidine and its prodrug molnupiravir are being studied for its activity against a number of viral infections including influenza, MERS-CoV, and SARS-CoV-2.

Molnupiravir is approved in the UK for reducing the risk of hospitalization and death in mild to moderate COVID-19 cases for patients at increased risk of severe disease (eg. with obesity, diabetes mellitus, heart disease, or are over 60 years old).

In the US, molnupiravir is authorized for emergency use for the treatment of high-risk adults With mild to moderate COVID-19.