Authors: Jayk Bernal A, da silva G, Musungaie DB, Kovalchuk A, Brown ML, Assaid C PMID: 34914868 PMCID: PMC8693688 DOI: 10.1056/NEJMoa2116044 Abstract Background: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 [...]

Authors: Malone B, Campbell EA PMID: 34518697 DOI: 10.1038/s41594-021-00657-8 Abstract Molnupiravir, a wide-spectrum antiviral that is currently in phase 2/3 clinical trials for the treatment of COVID-19, is proposed to inhibit viral replication by a mechanism known as ‘lethal mutagenesis’. Two recently published studies reveal the biochemical and structural bases of how molnupiravir disrupts the [...]

Authors: Kabinger F, Stiller C, Schmitzova J, Kokic G PMID: 34381216 PMCID: PMC8437801 DOI: 10.1038/s41594-021-00651-0 Abstract Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, [...]

Authors: Zhou S, Hill CS, Sarkar S, Tse LV, Woodburn BM PMID: 33961695 PMCID: PMC8136050 DOI: 10.1093/infdis/jiab247 Abstract Mutagenic ribonucleosides can act as broad-based antiviral agents. They are metabolized to the active ribonucleoside triphosphate form and concentrate in genomes of RNA viruses during viral replication. β-d-N4-hydroxycytidine (NHC, initial metabolite of molnupiravir) is >100-fold more active [...]

Authors: Menendez-Arias L PMID: 34118236 PMCID: PMC8188802 DOI: 10.1016/j.jbc.2021.100867 Abstract Molnupiravir, a prodrug of the nucleoside derivative β-D-N4-hydroxycytidine (NHC), is currently in clinical trials for COVID-19 therapy. However, the biochemical mechanisms involved in molnupiravir-induced mutagenesis had not been explored. In a recent study, Gordon et al. demonstrated that NHC can be incorporated into viral RNA [...]