Cargando…

Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection

The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against S...

Descripción completa

Detalles Bibliográficos
Autores principales: de Wit, Emmie, Feldmann, Friederike, Cronin, Jacqueline, Jordan, Robert, Okumura, Atsushi, Thomas, Tina, Scott, Dana, Cihlar, Tomas, Feldmann, Heinz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104368/
https://www.ncbi.nlm.nih.gov/pubmed/32054787
http://dx.doi.org/10.1073/pnas.1922083117
_version_ 1783512222682578944
author de Wit, Emmie
Feldmann, Friederike
Cronin, Jacqueline
Jordan, Robert
Okumura, Atsushi
Thomas, Tina
Scott, Dana
Cihlar, Tomas
Feldmann, Heinz
author_facet de Wit, Emmie
Feldmann, Friederike
Cronin, Jacqueline
Jordan, Robert
Okumura, Atsushi
Thomas, Tina
Scott, Dana
Cihlar, Tomas
Feldmann, Heinz
author_sort de Wit, Emmie
collection PubMed
description The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV−induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.
format Online
Article
Text
id pubmed-7104368
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher National Academy of Sciences
record_format MEDLINE/PubMed
spelling pubmed-71043682020-04-02 Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection de Wit, Emmie Feldmann, Friederike Cronin, Jacqueline Jordan, Robert Okumura, Atsushi Thomas, Tina Scott, Dana Cihlar, Tomas Feldmann, Heinz Proc Natl Acad Sci U S A Biological Sciences The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV−induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV. National Academy of Sciences 2020-03-24 2020-02-13 /pmc/articles/PMC7104368/ /pubmed/32054787 http://dx.doi.org/10.1073/pnas.1922083117 Text en Copyright © 2020 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
de Wit, Emmie
Feldmann, Friederike
Cronin, Jacqueline
Jordan, Robert
Okumura, Atsushi
Thomas, Tina
Scott, Dana
Cihlar, Tomas
Feldmann, Heinz
Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
title Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
title_full Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
title_fullStr Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
title_full_unstemmed Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
title_short Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
title_sort prophylactic and therapeutic remdesivir (gs-5734) treatment in the rhesus macaque model of mers-cov infection
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104368/
https://www.ncbi.nlm.nih.gov/pubmed/32054787
http://dx.doi.org/10.1073/pnas.1922083117
work_keys_str_mv AT dewitemmie prophylacticandtherapeuticremdesivirgs5734treatmentintherhesusmacaquemodelofmerscovinfection
AT feldmannfriederike prophylacticandtherapeuticremdesivirgs5734treatmentintherhesusmacaquemodelofmerscovinfection
AT croninjacqueline prophylacticandtherapeuticremdesivirgs5734treatmentintherhesusmacaquemodelofmerscovinfection
AT jordanrobert prophylacticandtherapeuticremdesivirgs5734treatmentintherhesusmacaquemodelofmerscovinfection
AT okumuraatsushi prophylacticandtherapeuticremdesivirgs5734treatmentintherhesusmacaquemodelofmerscovinfection
AT thomastina prophylacticandtherapeuticremdesivirgs5734treatmentintherhesusmacaquemodelofmerscovinfection
AT scottdana prophylacticandtherapeuticremdesivirgs5734treatmentintherhesusmacaquemodelofmerscovinfection
AT cihlartomas prophylacticandtherapeuticremdesivirgs5734treatmentintherhesusmacaquemodelofmerscovinfection
AT feldmannheinz prophylacticandtherapeuticremdesivirgs5734treatmentintherhesusmacaquemodelofmerscovinfection