Cargando…

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

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....

Descripción completa

Detalles Bibliográficos
Autores principales: Johnson, Dylan M., Brasel, Trevor, Massey, Shane, Garron, Tania, Grimes, Michael, Smith, Jeanon, Torres, Maricela, Wallace, Shannon, Villasante-Tezanos, Alejandro, Beasley, David W., Comer, Jason E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Authors. Published by Elsevier B.V. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9756747/
https://www.ncbi.nlm.nih.gov/pubmed/36535309
http://dx.doi.org/10.1016/j.antiviral.2022.105492
_version_ 1784851684419174400
author Johnson, Dylan M.
Brasel, Trevor
Massey, Shane
Garron, Tania
Grimes, Michael
Smith, Jeanon
Torres, Maricela
Wallace, Shannon
Villasante-Tezanos, Alejandro
Beasley, David W.
Comer, Jason E.
author_facet Johnson, Dylan M.
Brasel, Trevor
Massey, Shane
Garron, Tania
Grimes, Michael
Smith, Jeanon
Torres, Maricela
Wallace, Shannon
Villasante-Tezanos, Alejandro
Beasley, David W.
Comer, Jason E.
author_sort Johnson, Dylan M.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9756747
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher The Authors. Published by Elsevier B.V.
record_format MEDLINE/PubMed
spelling pubmed-97567472022-12-16 Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model Johnson, Dylan M. Brasel, Trevor Massey, Shane Garron, Tania Grimes, Michael Smith, Jeanon Torres, Maricela Wallace, Shannon Villasante-Tezanos, Alejandro Beasley, David W. Comer, Jason E. Antiviral Res Article 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. The Authors. Published by Elsevier B.V. 2023-01 2022-12-16 /pmc/articles/PMC9756747/ /pubmed/36535309 http://dx.doi.org/10.1016/j.antiviral.2022.105492 Text en © 2022 The Authors Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Johnson, Dylan M.
Brasel, Trevor
Massey, Shane
Garron, Tania
Grimes, Michael
Smith, Jeanon
Torres, Maricela
Wallace, Shannon
Villasante-Tezanos, Alejandro
Beasley, David W.
Comer, Jason E.
Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model
title Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model
title_full Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model
title_fullStr Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model
title_full_unstemmed Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model
title_short Evaluation of molnupiravir (EIDD-2801) efficacy against SARS-CoV-2 in the rhesus macaque model
title_sort evaluation of molnupiravir (eidd-2801) efficacy against sars-cov-2 in the rhesus macaque model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9756747/
https://www.ncbi.nlm.nih.gov/pubmed/36535309
http://dx.doi.org/10.1016/j.antiviral.2022.105492
work_keys_str_mv AT johnsondylanm evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel
AT braseltrevor evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel
AT masseyshane evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel
AT garrontania evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel
AT grimesmichael evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel
AT smithjeanon evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel
AT torresmaricela evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel
AT wallaceshannon evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel
AT villasantetezanosalejandro evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel
AT beasleydavidw evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel
AT comerjasone evaluationofmolnupiravireidd2801efficacyagainstsarscov2intherhesusmacaquemodel