Evaluation of SSYA10-001 as a replication inhibitor of severe acute respiratory syndrome, mouse hepatitis, and Middle East respiratory syndrome coronaviruses

Antimicrob Agents Chemother. 2014 Aug;58(8):4894-8. doi: 10.1128/AAC.02994-14. Epub 2014 May 19.

Abstract

We have previously shown that SSYA10-001 blocks severe acute respiratory syndrome coronavirus (SARS-CoV) replication by inhibiting SARS-CoV helicase (nsp13). Here, we show that SSYA10-001 also inhibits replication of two other coronaviruses, mouse hepatitis virus (MHV) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). A putative binding pocket for SSYA10-001 was identified and shown to be similar in SARS-CoV, MERS-CoV, and MHV helicases. These studies show that it is possible to target multiple coronaviruses through broad-spectrum inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Binding Sites
  • Cell Line
  • Chlorocebus aethiops
  • DNA Helicases / antagonists & inhibitors*
  • DNA Helicases / chemistry
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects
  • Fibroblasts / pathology
  • Fibroblasts / virology
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Middle East Respiratory Syndrome Coronavirus / drug effects*
  • Middle East Respiratory Syndrome Coronavirus / physiology
  • Molecular Docking Simulation
  • Molecular Sequence Data
  • Murine hepatitis virus / drug effects*
  • Murine hepatitis virus / physiology
  • Protein Binding
  • SARS Virus / drug effects*
  • SARS Virus / physiology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Triazoles / chemistry
  • Triazoles / pharmacology*
  • Vero Cells
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / chemistry
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • SSYA10-001
  • Triazoles
  • Viral Proteins
  • DNA Helicases