EDP-938, a Novel Nucleoprotein Inhibitor of Respiratory Syncytial Virus, Demonstrates Potent Antiviral Activities in Vitro and in a Non-human Primate Model

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2021 Mar 15

PMID 33720995

Citations 12

Authors

Michael H J Rhodin

Nicole V McAllister

Jonathan Castillo

Sarah L Noton

Rachel Fearns

In Jong Kim

Jianming Yu

Thomas P Blaisdell

Joseph Panarese

Brian C Shook

Yat Sun Or

Bryan Goodwin

Kai Lin

Affiliations

Soon will be listed here.

Abstract

EDP-938 is a novel non-fusion replication inhibitor of respiratory syncytial virus (RSV). It is highly active against all RSV-A and B laboratory strains and clinical isolates tested in vitro in various cell lines and assays, with half-maximal effective concentrations (EC50s) of 21, 23 and 64 nM against Long (A), M37 (A) and VR-955 (B) strains, respectively, in the primary human bronchial epithelial cells (HBECs). EDP-938 inhibits RSV at a post-entry replication step of the viral life cycle as confirmed by time-of-addition study, and the activity appears to be mediated by viral nucleoprotein (N). In vitro resistance studies suggest that EDP-938 presents a higher barrier to resistance compared to viral fusion or non-nucleoside L polymerase inhibitors with no cross-resistance observed. Combinations of EDP-938 with other classes of RSV inhibitors lead to synergistic antiviral activity in vitro. Finally, EDP-938 has also been shown to be efficacious in vivo in a non-human primate model of RSV infection.

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