Title: Determining a Hepatitis Delta virus (HDV) peptidomimetic therapeutic to target Hepatitis B virus (HBV)
Background: Hepatitis Delta virus is a defective RNA virus that requires HBV surface proteins to complete its replication. ~5% of HBV-infected individuals also have HDV. Clinically, HBV DNA levels are lower in HBV-HDV co-infection compared to HBV mono-infection. The HDV genome encodes two proteins, the small hepatitis D (SHD) antigen, and the large hepatitis D (LHD) antigen. These proteins can bind HBV pgRNA which is sufficient to lower HBV levels.
Purpose: To characterize the structural interaction between the SHD/LHD and HBV pgRNA.
Methods: HDV proteins were recombinantly produced in E. coli and purified via affinity and size exclusion chromatography. A segment of pgRNA (consensus determined from >13,000 HBV reference sequences) will be produced by in vitro transcription. Binding studies using microscale thermophoresis will follow.
Results: Recombinant HDV proteins have been produced. The consensus sequence of HBV RNA’s segment of interest has been determined and production is underway.
Conclusion: Understanding how HDV and HBV interact at the molecular level may provide insight into novel approaches to targeting HBV.