Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge
Science Translational Medicine • 29 May 2019 • Vol 11, Issue 494 • DOI: 10.1126/scitranslmed.aau9242
Nipping Nipah virus infections in the bud
Human infection with Nipah virus is often fatal, and there are no approved therapeutics. Lo et al. tested the nucleotide prodrug remdesivir (GS-5734), which has shown activity against other pathogens such as Ebola virus, in a nonhuman primate model. Animals were administered a lethal dose of Nipah virus, and half were treated daily with remdesivir starting 24 hours later. All control animals had to be euthanized, and although treated animals had some mild symptoms, all survived. These results indicate that efficacy of remdesivir should be tested in human Nipah virus infection.
Abstract
Nipah virus is an emerging pathogen in the Paramyxoviridae family. Upon transmission of Nipah virus from its natural reservoir, Pteropus spp. fruit bats, to humans, it causes respiratory and neurological disease with a case-fatality rate about 70%. Human-to-human transmission has been observed during Nipah virus outbreaks in Bangladesh and India. A therapeutic treatment for Nipah virus disease is urgently needed. Here, we tested the efficacy of remdesivir (GS-5734), a broad-acting antiviral nucleotide prodrug, against Nipah virus Bangladesh genotype in African green monkeys. Animals were inoculated with a lethal dose of Nipah virus, and a once-daily intravenous remdesivir treatment was initiated 24 hours later and continued for 12 days. Mild respiratory signs were observed in two of four treated animals, whereas all control animals developed severe respiratory disease signs. In contrast to control animals, which all succumbed to the infection, all remsdesivir-treated animals survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment for Nipah virus infection.
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Supplementary Material
Summary
Fig. S1. Nipah virus antigen in the CNS of one of four remdesivir-treated AGMs.
Fig. S2. Determination of virus neutralizing antibody titer against Nipah virus Bangladesh.
Data file S1. Primary data.
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Information & Authors
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Published In
Science Translational Medicine
Volume 11 | Issue 494
May 2019
May 2019
Copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
This is an article distributed under the terms of the Science Journals Default License.
Submission history
Received: 27 July 2018
Accepted: 17 April 2019
Acknowledgments
We thank the members of the Rocky Mountain Veterinary Branch (DIR, NIAID, and NIH) for their assistance with this study; D. Porter for critical review of the manuscript; and B. Bollweg for IHC assistance. Funding: This work is supported by the Intramural Research Program of NIAID, NIH (to F.F., J.C., H.F., and E.d.W.) and by core funding at CDC (to M.K.L., J.M.G., N.R.P., J.D.K., S.T.N., S.R.Z., and C.F.S.). Author contributions: M.K.L., R.J., H.F., S.T.N., T.C., C.F.S., and E.d.W. conceived the studies. M.K.L., F.F., J.M.G., J.C., N.R.P., S.R.Z., and E.d.W. collected the data. M.K.L., F.F., J.M.G., R.J., R.B., J.C., N.R.P., J.D.K., S.T.N., T.C., S.R.Z., H.F., C.F.S., and E.d.W. interpreted the data. M.K.L. and E.d.W. wrote the manuscript. All authors read and corrected the manuscript. Competing interests: 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 CDC and NIH have no conflict of interests to report. Data and materials availability: All data associated with this study are present in the paper or the Supplementary Materials.
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