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RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
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3-Hydroxypyrimidine-2,4-Diones as Novel Hepatitis B Virus Antivirals Targeting the Viral Ribonuclease H.

Andrew D Huber, Eleftherios Michailidis, Jing Tang, Maritza N Puray-Chavez, Maria Boftsi, Jennifer J Wolf, Kelsey N Boschert, Megan A Sheridan, Maxwell D Leslie, Karen A Kirby, Kamalendra Singh, Hiroaki Mitsuya, Michael A Parniak, Zhengqiang Wang, Stefan G Sarafianos
Antimicrobial Agents and Chemotherapy 2017 June
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.

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