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

## TL;DR

This study tested MSD-914, a drug that inhibits a specific enzyme, in mice and rhesus macaques to see if it can protect against Ebola virus.

## Contribution

The study reveals that MSD-914, effective in mice, failed to protect rhesus macaques from Ebola despite similar drug exposure.

## Key findings

- MSD-914 protected mice from Ebola at low oral doses.
- Despite similar drug exposure, MSD-914 did not protect rhesus macaques from Ebola.
- The drug's efficacy varied significantly between mouse and primate models.

## 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.