EDP-938, a novel nucleoprotein inhibitor of respiratory syncytial virus, demonstrates potent antiviral activities in vitro and in a non-human primate model

PLoS Pathog. 2021 Mar 15;17(3):e1009428. doi: 10.1371/journal.ppat.1009428. eCollection 2021 Mar.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Epithelial Cells / drug effects
  • Epithelial Cells / virology
  • Humans
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / virology
  • Respiratory Syncytial Virus Infections*
  • Respiratory Syncytial Virus, Human / drug effects


  • Antiviral Agents

Grants and funding

Enanta Pharmaceuticals Inc. (https://www.enanta.com) was the sole organization responsible for the funding of all the research presented here. Enanta Pharmaceuticals owns the intellectual property rights for EDP-938. No grant numbers are associated with any of this work. Authors' MR, NM, JC, IJK, JY, TB, JP, BS, YSO, BG, and KL were employees of Enanta Pharmaceuticals and received salary and benefits compensation during the course of this work. Authors SN and RF were paid by Enanta Pharmaceuticals for their work performing assays whose data have been included in this manuscript.