Hepatitis B virus (HBV) RNase H (RNH) is an appealing therapeutic target due to its essential role in viral replication. RNH inhibitors (RNHIs) could help to more effectively control HBV infections. Here, we report 3-hydroxypyrimidine-2,4- diones as novel HBV RNHIs with antiviral activity. We synthesized and tested 52 analogs and found 4 that inhibit HBV RNH activity in infected cells. Importantly, 2 of these compounds inhibited HBV replication in the low micromolar range.
Bibliographical noteFunding Information:
This work was supported in part by grants from the National Institutes of Health (NIH) (AI100890 and AI121315 to S.G.S. and Z.W.) and Trail to a Cure. A.D.H. is supported by NIH grant AI100890-S1, M.N.P.-C. is supported by the Fulbright Student Program, and J.J.W. is supported by a Life Sciences Fellowship from the University of Missouri. We also acknowledge partial support from Kumamoto University and the Japan Agency for Medical Research and Development.
© 2017 American Society for Microbiology. All Rights Reserved.
- Antiviral agents
- Hepatitis B virus
- Rnase H