title: SB 9200, a novel agonist of innate immunity, shows potent antiviral activity against resistant HCV variants.
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.
authors.affiliation: The Liver Unit, Blizard Institute, Barts Health, Queen Mary University of London, London, UK.
authors.forename: Meleri
authors.identifier: 0000-0001-9158-2971
authors.initials: M
authors.lastname: Jones
authors.affiliation: The Liver Unit, Blizard Institute, Barts Health, Queen Mary University of London, London, UK.
authors.forename: Morven E
authors.initials: ME
authors.lastname: Cunningham
authors.affiliation: The Liver Unit, Blizard Institute, Barts Health, Queen Mary University of London, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Wing
authors.affiliation: The Liver Unit, Blizard Institute, Barts Health, Queen Mary University of London, London, UK.
authors.forename: Sampath
authors.initials: S
authors.lastname: DeSilva
authors.affiliation: Spring Bank Pharmaceuticals, Milford, Massachusetts.
authors.forename: Rupa
authors.initials: R
authors.lastname: Challa
authors.affiliation: Spring Bank Pharmaceuticals, Milford, Massachusetts.
authors.forename: Anjaneyulu
authors.initials: A
authors.lastname: Sheri
authors.affiliation: Spring Bank Pharmaceuticals, Milford, Massachusetts.
authors.forename: Seetharamaiyer
authors.initials: S
authors.lastname: Padmanabhan
authors.affiliation: Spring Bank Pharmaceuticals, Milford, Massachusetts.
authors.forename: Radhakrishnan P
authors.initials: RP
authors.lastname: Iyer
authors.affiliation: Department of Microbiology & Immunology, Georgetown University Medical Centre, Washington, District of Columbia.
authors.forename: Brent E
authors.initials: BE
authors.lastname: Korba
authors.affiliation: Department of Microbiology & Immunology, Georgetown University Medical Centre, Washington, District of Columbia.
authors.forename: Nezam
authors.initials: N
authors.lastname: Afdhal
authors.affiliation: The Liver Unit, Blizard Institute, Barts Health, Queen Mary University of London, London, UK.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000821:virology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
chemical_list: D000998:Antiviral Agents; D007155:Immunologic Factors
keywords: antiviral agents; disease control, anti-hepatitis C virus DAA (directly acting antivirals); hepatitis C virus; virus classification, antiviral agents