Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model

Antiviral Res. 2023 Jan:209:105492. doi: 10.1016/j.antiviral.2022.105492. Epub 2022 Dec 16.

Abstract

Molnupiravir (EIDD-2801) is a prodrug of a ribonucleoside analogue that is currently being used under a US FDA emergency use authorization for the treatment of mild to moderate COVID-19. We evaluated molnupiravir for efficacy as an oral treatment in the rhesus macaque model of SARS-CoV-2 infection. Twenty non-human primates (NHPs) were challenged with SARS-CoV-2 and treated with 75 mg/kg (n = 8) or 250 mg/kg (n = 8) of molnupiravir twice daily by oral gavage for 7 days. The NHPs were observed for 14 days post-challenge and monitored for clinical signs of disease. After challenge, all groups showed a trend toward increased respiration rates. Treatment with molnupiravir significantly reduced viral RNA levels in bronchoalveolar lavage (BAL) samples at Days 7 and 10. Considering the mild to moderate nature of SARS-CoV-2 infection in the rhesus macaque model, this study highlights the importance of monitoring the viral load in the lung as an indicator of pharmaceutical efficacy for COVID-19 treatments. Additionally, this study provides evidence of the efficacy of molnupiravir which supplements the current ongoing clinical trials of this drug.

Keywords: COVID-19; EIDD-2801; Molnupiravor; Non-human primate; Rhesus macaque; SARS-CoV-2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • COVID-19*
  • Cytidine / pharmacology
  • Cytidine / therapeutic use
  • Macaca mulatta
  • SARS-CoV-2*

Substances

  • molnupiravir
  • Cytidine