SB 9200, a novel agonist of innate immunity, shows potent antiviral activity against resistant HCV variants

J Med Virol. 2017 Sep;89(9):1620-1628. doi: 10.1002/jmv.24809. Epub 2017 May 23.

Abstract

SB 9200 is a novel, first-in-class oral modulator of innate immunity that is believed to act via the activation of the RIG-I and NOD2 pathways. SB 9200 has broad-spectrum antiviral activity against RNA viruses including hepatitis C virus (HCV), norovirus, respiratory syncytial virus, and influenza and has demonstrated activity against hepatitis B virus (HBV) in vitro and in vivo. In phase I clinical trials in chronically infected HCV patients, SB 9200 has been shown to reduce HCV RNA by up to 1.9 log10 . Here, we demonstrate the antiviral activity of SB 9200 against a HCV replicon system and patient derived virus. Using the HCV capture-fusion assay, we show that SB 9200 is active against diverse HCV genotypes and is also effective against HCV derived from patients who relapse following direct-acting antiviral treatment, including viruses containing known NS5A resistance-associated sequences. These data confirm the broad antiviral activity of SB 9200 and indicate that it may have clinical utility in HCV patients who have failed to respond to current antiviral regimens.

Keywords: antiviral agents; disease control, anti-hepatitis C virus DAA (directly acting antivirals); hepatitis C virus; virus classification, antiviral agents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiviral Agents / pharmacology*
  • Genotype
  • Hepacivirus / classification
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / virology
  • Humans
  • Immunologic Factors / pharmacology*
  • Microbial Sensitivity Tests

Substances

  • Antiviral Agents
  • Immunologic Factors