Antiviral Efficacy and Host Innate Immunity Associated with SB 9200 Treatment in the Woodchuck Model of Chronic Hepatitis B

• DOI: 10.1371/journal.pone.0161313
• Publication Date: 2016-08-23T17:39:48Z
• Authors: Kyle E. Korolowicz; Radhakrishnan P. ...; Stefanie Czerwinski; Manasa Suresh; Junming Yang; Seetharamaiyer Pa...; Anjaneyulu Sheri; Rajendra K. Pandey; Jeffrey Skell; Judith K. Marquis; Bhaskar V. Kallakury; Robin D. Tucker; Stephan Menne
• Keywords: Woodchuck hepatitis virus; Antiviral protein

SB 9200, an oral prodrug of the dinucleotide 9000, is being developed for treatment chronic hepatitis B virus (HBV) infection and represents a novel class antivirals. 9200 thought to activate viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) nucleotide-binding oligomerization domain-containing protein 2 (NOD2) resulting in interferon (IFN) mediated antiviral immune responses virus-infected cells. Additionally, binding these proteins could also sterically block ability polymerase access pre-genomic RNA nucleic acid synthesis. The stimulating direct properties were evaluated woodchucks chronically infected with woodchuck (WHV) by daily, dosing at 15 30 mg/kg 12 weeks. Prolonged resulted 2.2 3.7 log10 reductions serum WHV DNA 0.5 1.6 declines surface antigen from pretreatment level lower or higher dose respectively. hepatic levels acids reduced liver inflammation. Following cessation, recrudescence replication was observed but dose-dependent delays relapse. effects associated long-lasting induction IFN-α, IFN-β IFN-stimulated genes blood liver, which correlated prolonged activation RIG-I/NOD2 pathway presence elevated RIG-I levels. These results suggest that addition activity, induces immunity during hepadnaviral via pathway.