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

doi:10.1128/AAC.00245-17

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

Center for Drug Design

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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.

Original language	English (US)
Article number	e00245-17
Journal	Antimicrobial agents and chemotherapy
Volume	61
Issue number	6
DOIs	https://doi.org/10.1128/AAC.00245-17
State	Published - Jun 2017

Bibliographical note

Funding 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.

Publisher Copyright:
© 2017 American Society for Microbiology. All Rights Reserved.

Keywords

Antiviral agents
Hepatitis B virus
Rnase H

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444124

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Huber, A. D., Michailidis, E., Tang, J., Puray-Chavez, M. N., Boftsi, M., Wolf, J. J., Boschert, K. N., Sheridan, M. A., Leslie, M. D., Kirby, K. A., Singh, K., Mitsuya, H., Parniak, M. A., Wang, Z., & Sarafianos, S. G. (2017). 3-hydroxypyrimidine-2,4-diones as novel hepatitis b virus antivirals targeting the viral ribonuclease H. Antimicrobial agents and chemotherapy, 61(6), Article e00245-17. https://doi.org/10.1128/AAC.00245-17

Huber, AD, Michailidis, E, Tang, J, Puray-Chavez, MN, Boftsi, M, Wolf, JJ, Boschert, KN, Sheridan, MA, Leslie, MD, Kirby, KA, Singh, K, Mitsuya, H, Parniak, MA, Wang, Z & Sarafianos, SG 2017, '3-hydroxypyrimidine-2,4-diones as novel hepatitis b virus antivirals targeting the viral ribonuclease H', Antimicrobial agents and chemotherapy, vol. 61, no. 6, e00245-17. https://doi.org/10.1128/AAC.00245-17

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3-hydroxypyrimidine-2,4-diones as novel hepatitis b virus antivirals targeting the viral ribonuclease H

Abstract

Bibliographical note

Keywords

UN SDGs

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