Developing a direct acting, orally available antiviral agent in a pandemic: the evolution of molnupiravir as a potential treatment for COVID-19

• Type of Material: Article
• Authors: George Painter, Emory University; Michael Natchus, Emory University; Oren Cohen, Covance Clinical Research Unit Ltd; Wendy Holman, Ridgeback Biotherapeut LP
• Language: English
• Date: 2021-07-13
• Publisher: ELSEVIER SCI LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Elsevier B.V. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.coviro.2021.06.003
• Title of Journal or Parent Work: CURRENT OPINION IN VIROLOGY
• Volume: 50
• Start Page: 17
• End Page: 22
• Grant/Funding Information: Much of the work discussed in this manuscript was supported by the Defense Threat Reduction Agency [contracts HDTRA1-13-C-0072 and HDTRA1-15-C-0075] and by the National Institute of Allergy and Infectious Disease [contracts HHSN272201500008C and 75N93019C00058 and grant SP00013673-01].
• Keywords: Life Sciences & Biomedicine; Virology; ANALOGS; VENEZUELAN EQUINE ENCEPHALITIS; MICE; Science & Technology; INFECTION; VIRUS; RNA; NUCLEOSIDE; REPLICATION
• Research Categories: Health Sciences, Pharmacology

Abstract

Despite the availability of vaccines, there remains an urgent need for antiviral drugs with potent activity against SARS-CoV-2, the cause of COVID-19. Millions of people are immune-suppressed and may not be able to mount a fully protective immune response after vaccination. There is also an increasingly critical need for a drug to cover emerging SARS-CoV-2 variants, against which existing vaccines may be less effective. Here, we describe the evolution of molnupiravir (EIDD-2801, MK-4482), a broad-spectrum antiviral agent originally designed for the treatment of Alphavirus infections, into a potential drug for the prevention and treatment of COVID-19. When the pandemic began, molnupiravir was in pre-clinical development for the treatment of seasonal influenza. As COVID-19 spread, the timeline for the development program was moved forward significantly, and focus shifted to treatment of coronavirus infections. Real time consultation with regulatory authorities aided in making the acceleration of the program possible.