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3-Hydroxypyrimidine-2,4-Diones as Novel Hepatitis B Virus Antivirals Targeting the Viral Ribonuclease H.

ABSTRACT: 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.

SUBMITTER: Huber AD

PROVIDER: S-EPMC5444124 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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3-Hydroxypyrimidine-2,4-Diones as Novel Hepatitis B Virus Antivirals Targeting the Viral Ribonuclease H.

Huber Andrew D AD Michailidis Eleftherios E Tang Jing J Puray-Chavez Maritza N MN Boftsi Maria M Wolf Jennifer J JJ Boschert Kelsey N KN Sheridan Megan A MA Leslie Maxwell D MD Kirby Karen A KA Singh Kamalendra K Mitsuya Hiroaki H Parniak Michael A MA Wang Zhengqiang Z Sarafianos Stefan G SG

Antimicrobial agents and chemotherapy 20170524 6

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. ...[more]

PMID: 28320718

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3-Hydroxypyrimidine-2,4-diones as an inhibitor scaffold of HIV integrase.

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