Inhibition of HBV replication by N-hydroxyisoquinolinedione and N-hydroxypyridinedione ribonuclease H inhibitors.

ABSTRACT: We recently developed a screening system capable of identifying and evaluating inhibitors of the Hepatitis B virus (HBV) ribonuclease H (RNaseH), which is the only HBV enzyme not targeted by current anti-HBV therapies. Inhibiting the HBV RNaseH blocks synthesis of the positive-polarity DNA strand, causing early termination of negative-polarity DNA synthesis and accumulation of RNA:DNA heteroduplexes. We previously reported inhibition of HBV replication by N-hydroxyisoquinolinediones (HID) and N-hydroxypyridinediones (HPD) in human hepatoma cells. Here, we report results from our ongoing efforts to develop more potent anti-HBV RNaseH inhibitors in the HID/HPD compound classes. We synthesized and screened additional HIDs and HPDs for preferential suppression of positive-polarity DNA in cells

SUBMITTER: Edwards TC 

PROVIDER: S-EPMC10587990 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature