The enterovirus 3C protease inhibitor SG85 efficiently blocks rhinovirus replication and is not cross-resistant with rupintrivir

Antimicrob Agents Chemother. 2015 Sep;59(9):5814-8. doi: 10.1128/AAC.00534-15. Epub 2015 Jun 8.

Abstract

The novel enterovirus protease inhibitor (PI) SG85 effectively inhibits the in vitro replication of 14 rhinoviruses representative of species A and B (median 50% effective concentration, 0.04 μM). A low-level SG85-resistant variant was selected that carried amino acid substitutions S127G and T143A in the 3C protease. Both substitutions are required for low-level resistance to SG85, as demonstrated by reverse genetics. Interestingly, there is no cross-resistance to SG85 and rupintrivir (another PI); a structural explanation is provided for this observation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Drug Resistance, Viral
  • Enterovirus / drug effects
  • Enterovirus / enzymology*
  • Isoxazoles / pharmacology*
  • Phenylalanine / analogs & derivatives
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Pyrrolidinones / pharmacology*
  • Valine / analogs & derivatives
  • Viral Proteins / antagonists & inhibitors
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Isoxazoles
  • Protease Inhibitors
  • Pyrrolidinones
  • Viral Proteins
  • Phenylalanine
  • Valine
  • rupintrivir