Hepatitis B Virus Ribonuclease H: Mechanisms of Catalysis and Inhibition
Abstract
Hepatitis B Virus (HBV) causes chronic hepatitis, cirrhosis, liver failure, and liver cancer, but current drugs cannot fully control viral replication or stop disease progression. HBV replicates by reverse transcription. The viral ribonuclease H (RNaseH) is needed to remove the viral RNA after it has been copied into the first DNA strand so that the second DNA strand can be made. Failure of RNaseH action causes viral DNA replication to fail. Despite being essential for viral replication and being an obvious drug target, the HBV RNaseH is uncharacterized because it only recently became possible to purify active enzyme. This project will generate the first in-depth biochemical data about function and inhibition of the RNaseH. Specifically, it will define the interaction between the RNaseH and its Mg++ ion cofactor, assess binding between the RNaseH and its substrate, define the mechanism of inhibition induced by multiple classes of RNaseH inhibitors, and provide the first structure-function analysis of the enzyme.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1148034
Entities
People
- John E Tavis
- Nicola Pozzi
Organizations
- Saint Louis University