Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

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

View ORCID ProfileEmmie de Wit, Friederike Feldmann, Jacqueline Cronin, Robert Jordan, Atsushi Okumura, Tina Thomas, Dana Scott, Tomas Cihlar, and Heinz Feldmann
PNAS March 24, 2020 117 (12) 6771-6776; first published February 13, 2020; https://doi.org/10.1073/pnas.1922083117
Emmie de Wit
aLaboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Emmie de Wit
  • For correspondence: Emmie.deWit@nih.gov
Friederike Feldmann
bRocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacqueline Cronin
aLaboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert Jordan
cBiology Department, Gilead Sciences, Foster City, CA 94404;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Atsushi Okumura
dCenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tina Thomas
aLaboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dana Scott
bRocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tomas Cihlar
cBiology Department, Gilead Sciences, Foster City, CA 94404;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heinz Feldmann
aLaboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  1. Edited by Michael B. A. Oldstone, Scripps Research Institute, La Jolla, CA, and approved February 7, 2020 (received for review December 16, 2019)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

Middle East Respiratory Syndrome, caused by the MERS coronavirus (MERS-CoV), continues to cause severe respiratory disease with a high case fatality rate. To date, potential antiviral treatments for MERS-CoV have shown limited efficacy in animal studies. Here, we tested the efficacy of the broad-acting antiviral remdesivir in the rhesus macaque model of MERS-CoV infection. Remdesivir reduced the severity of disease, virus replication, and damage to the lungs when administered either before or after animals were infected with MERS-CoV. Our data show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials. It may also have utility for related coronaviruses such as the novel coronavirus 2019-nCoV emerging from Wuhan, China.

Abstract

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.

  • MERS-CoV
  • antiviral
  • animal model
  • remdesivir
  • therapy

Footnotes

  • ↵1To whom correspondence may be addressed. Email: Emmie.deWit{at}nih.gov.
  • Author contributions: E.d.W., R.J., and H.F. designed research; E.d.W., F.F., J.C., A.O., T.T., and D.S. performed research; T.C. contributed new reagents/analytic tools; E.d.W., A.O., and D.S. analyzed data; E.d.W. and H.F. wrote the paper; and F.F., J.C., R.J., A.O., T.T., D.S., and T.C. read and approved the manuscript.

  • Competing interest statement: The authors affiliated with Gilead Sciences are employees of the company and may own company stock; R.J. holds a patent on the use of remdesivir to treat Filovirus infections. The authors affiliated with NIH have no conflict of interest to report.

  • This article is a PNAS Direct Submission.

  • Data deposition: All data discussed here will be made available to readers upon request.

  • This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1922083117/-/DCSupplemental.

  • Copyright © 2020 the Author(s). Published by PNAS.

This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
Emmie de Wit, Friederike Feldmann, Jacqueline Cronin, Robert Jordan, Atsushi Okumura, Tina Thomas, Dana Scott, Tomas Cihlar, Heinz Feldmann
Proceedings of the National Academy of Sciences Mar 2020, 117 (12) 6771-6776; DOI: 10.1073/pnas.1922083117

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
Emmie de Wit, Friederike Feldmann, Jacqueline Cronin, Robert Jordan, Atsushi Okumura, Tina Thomas, Dana Scott, Tomas Cihlar, Heinz Feldmann
Proceedings of the National Academy of Sciences Mar 2020, 117 (12) 6771-6776; DOI: 10.1073/pnas.1922083117
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 117 (12)
Table of Contents

Submit

Sign up for Article Alerts

Article Classifications

  • Biological Sciences
  • Microbiology

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Materials and Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Abstract depiction of a guitar and musical note
Science & Culture: At the nexus of music and medicine, some see disease treatments
Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s.
Image credit: Shutterstock/agsandrew.
Scientist looking at an electronic tablet
Opinion: Standardizing gene product nomenclature—a call to action
Biomedical communities and journals need to standardize nomenclature of gene products to enhance accuracy in scientific and public communication.
Image credit: Shutterstock/greenbutterfly.
One red and one yellow modeled protein structures
Journal Club: Study reveals evolutionary origins of fold-switching protein
Shapeshifting designs could have wide-ranging pharmaceutical and biomedical applications in coming years.
Image credit: Acacia Dishman/Medical College of Wisconsin.
White and blue bird
Hazards of ozone pollution to birds
Amanda Rodewald, Ivan Rudik, and Catherine Kling talk about the hazards of ozone pollution to birds.
Listen
Past PodcastsSubscribe
Goats standing in a pin
Transplantation of sperm-producing stem cells
CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds.
Image credit: Jon M. Oatley.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Latest Articles
  • Archive

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490