Efficacy evaluation of the S-adenosylhomocysteine hydrolase inhibitor MSD-914 in rhesus macaques (Macaca Mulatta) challenged with Ebola virus by the intramuscular route

PLoS ONE 2026 Open access

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Authors: Sara C. Johnston, Anthony T. Ginnetti, Nancy A. Twenhafel, SARAH L.W. NORRIS, Shiying Chen, Josh L. Moore, Christopher W. Boyce, Ondraya M. Frick, Dave N. Dyer, Donald J. Marsh, Stephen C. Stevens, Walter F. Knapp
+17 more Kerry L. Berrier, Hui Wan, Gregory C. Adam, Timothy J. Hartingh, Heather L. Esham, Jimmy O. Fiallos, Eugene L. Blue, Willie B. Sifford, Jonathan D. Latty, Harold L. Mills, Nazira A. Alli, Ashley E. Piper, Aimee I. Goodson, J. Matthew Meinig, David B. Olsen, Linda A. Lieberman, Rekha G. Panchal
DOI: 10.1371/journal.pone.0340118
Cited by: 0
References: 18

Abstract

Ebola virus (EBOV) causes a severe and often fatal hemorrhagic fever in humans for which effective postexposure countermeasures are lacking. Herein, we describe the evaluation of an S-adenosylhomocysteine hydrolase inhibitor, MSD-914, using mouse and nonhuman primate (NHP) models of lethal EBOV. Mice were completely protected from severe disease and death at doses as low as 0.31 mg/kg/day administered orally. From the pharmacological data and a toxicokinetic study, a predicted protective dose was selected for rhesus macaques (RMs). Surprisingly, orally administered MSD-914 was unable to protect RMs at doses as high as 0.8 mg/kg/day despite providing similar exposure of the drug to the efficacious dose observed in the mouse model.

Fields of Study & Subjects

Viral Infections and Outbreaks Research Viral Infections and Vectors Poxvirus research and outbreaks

Publication details

Journal / source
PLoS ONE
Volume
21
Issue
2
Pages
e0340118–e0340118
Publication date
6 February 2026
Language
EN