{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:13:32Z","timestamp":1792199612305,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Molnupiravir is an oral prodrug of the broadly active, antiviral ribonucleoside analog <jats:italic>N<\/jats:italic>\u2010hydroxycytidine (NHC). The primary circulating metabolite NHC is taken up into cells and phosphorylated to NHC\u2010triphosphate (NHC\u2010TP). NHC\u2010TP serves as a competitive substrate for viral RNA\u2010dependent RNA polymerase (RdRp), which results in an accumulation of errors in the viral genome, rendering virus replication incompetent. Molnupiravir has demonstrated activity against SARS\u2010CoV\u20102 both clinically and preclinically and has a high barrier to development of viral resistance. Little to no molnupiravir is observed in plasma due to rapid hydrolysis to NHC. Maximum concentrations of NHC are reached at 1.5\u2009h following administration in a fasted state. The effective half\u2010life of NHC is 3.3\u2009h, reflecting minimal accumulation in the plasma following twice\u2010daily (Q12H) dosing. The terminal half\u2010life of NHC is 20.6\u2009h. NHC\u2010TP exhibits a flatter profile with a lower peak\u2010to\u2010trough ratio compared with NHC, which supports Q12H dosing. Renal and hepatic pathways are not major routes of elimination, as NHC is primarily cleared by metabolism to uridine and cytidine, which then mix with the endogenous nucleotide pools. In a phase III study of nonhospitalized patients with COVID\u201019 (MOVe\u2010OUT), 5\u2009days of treatment with 800\u2009mg molnupiravir Q12H significantly reduced the incidence of hospitalization or death compared with placebo. Patients treated with molnupiravir also had a greater reduction in SARS\u2010CoV\u20102 viral load and improved clinical outcomes, compared with those receiving placebo. The clinical effectiveness of molnupiravir has been further demonstrated in several real\u2010world evidence studies. Molnupiravir is currently authorized or approved in more than 25 countries.<\/jats:p>","DOI":"10.1111\/cts.13732","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T10:18:59Z","timestamp":1707387539000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Molnupiravir: Mechanism of action, clinical, and translational science"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2410-4379","authenticated-orcid":false,"given":"Brian M.","family":"Maas","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3893-9374","authenticated-orcid":false,"given":"Julie","family":"Strizki","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  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