EIDD-2801

EIDD-2801 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 EIDD-2801 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 is an orally bioavailable prodrug of EIDD-1931, the synthetic ribonucleoside derivative N4-hydroxycytidine and ribonucleoside analog, with potential antiviral activity against a variety of RNA viruses. Upon oral administration, molnupiravir, being a prodrug, is metabolized into its active form EIDD-1931 and converted into its triphosphate (TP) form. The TP form of EIDD-1931 is incorporated into RNA and inhibits the action of viral RNA-dependent RNA polymerase. This results in the termination of RNA transcription and decreases viral RNA production, and viral RNA replication.
Molnupiravir was originally developed as antiviral therapy for influenza. However, this antiviral has also shown activity against various other viruses, including SARS-CoV-2. The drug co-developed by Emory University, Ridgeback Biotherapeutics, and Merck is a promising oral treatment for COVID-19. The international nonproprietary name of the drug was inspired by that of Thor's hammer, Mjölnir. The idea is that the drug will strike down the virus like a mighty blow from the god of thunder.In 2019, the National Institute of Allergy and Infectious Diseases (NIAID) approved moving molnupiravir into Phase I clinical trials for influenza.In 2020, a study found that it is orally active against SARS-CoV-2 in ferrets. DRIVE then licensed molnupiravir for human clinical studies to Miami-based company Ridgeback Biotherapeutics, which later partnered with Merck & Co. to develop the drug further.
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 derives from a N(4)-hydroxycytidine.www.ebi.ac.uk