Literature DB >> 28320718

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

Andrew D Huber1,2, Eleftherios Michailidis1,3, Jing Tang4, Maritza N Puray-Chavez1,3, Maria Boftsi1,2, Jennifer J Wolf1,3, Kelsey N Boschert1,3, Megan A Sheridan1,5, Maxwell D Leslie1,3, Karen A Kirby1,3, Kamalendra Singh1,3, Hiroaki Mitsuya6,7,8, Michael A Parniak9, Zhengqiang Wang4, Stefan G Sarafianos10,3,5.   

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.
Copyright © 2017 American Society for Microbiology.

Entities:  

Keywords:  RNase H; antiviral agents; hepatitis B virus

Mesh：

Substances：

Year:  2017        PMID： 28320718      PMCID： PMC5444124          DOI： 10.1128/AAC.00245-17

Source DB:  PubMed          Journal:  Antimicrob Agents Chemother        ISSN： 0066-4804            Impact factor:   5.191


  22 in total

1.  3-Hydroxypyrimidine-2,4-diones as Selective Active Site Inhibitors of HIV Reverse Transcriptase-Associated RNase H: Design, Synthesis, and Biochemical Evaluations.

Authors:  Jing Tang; Feng Liu; Eva Nagy; Lena Miller; Karen A Kirby; Daniel J Wilson; Bulan Wu; Stefan G Sarafianos; Michael A Parniak; Zhengqiang Wang
Journal:  J Med Chem       Date:  2016-03-08       Impact factor: 7.446

2.  Hydroxylated tropolones inhibit hepatitis B virus replication by blocking viral ribonuclease H activity.

Authors:  Gaofeng Lu; Elena Lomonosova; Xiaohong Cheng; Eileen A Moran; Marvin J Meyers; Stuart F J Le Grice; Craig J Thomas; Jian-kang Jiang; Christine Meck; Danielle R Hirsch; Michael P D'Erasmo; Duygu M Suyabatmaz; Ryan P Murelli; John E Tavis
Journal:  Antimicrob Agents Chemother       Date:  2014-12-01       Impact factor: 5.191

Review 3.  Emerging pipeline drugs for hepatitis B infection.

Authors:  Natravis Cox; Hans Tillmann
Journal:  Expert Opin Emerg Drugs       Date:  2011-12       Impact factor: 4.191

4.  Hepatitis B virus nucleocapsid envelopment does not occur without genomic DNA synthesis.

Authors:  T Gerelsaikhan; J E Tavis; V Bruss
Journal:  J Virol       Date:  1996-07       Impact factor: 5.103

Review 5.  Development of novel therapeutics for chronic hepatitis B.

Authors:  You-hua Xie; Ran Hong; Wei Liu; Jing Liu; Jian-wei Zhai
Journal:  Virol Sin       Date:  2010-07-28       Impact factor: 4.327

6.  Relationship between viral DNA synthesis and virion envelopment in hepatitis B viruses.

Authors:  Y Wei; J E Tavis; D Ganem
Journal:  J Virol       Date:  1996-09       Impact factor: 5.103

7.  3-Hydroxypyrimidine-2,4-diones as an inhibitor scaffold of HIV integrase.

Authors:  Jing Tang; Kasthuraiah Maddali; Mathieu Metifiot; Yuk Y Sham; Robert Vince; Yves Pommier; Zhengqiang Wang
Journal:  J Med Chem       Date:  2011-03-07       Impact factor: 7.446

8.  6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase.

Authors:  Jing Tang; Kasthuraiah Maddali; Christine D Dreis; Yuk Y Sham; Robert Vince; Yves Pommier; Zhengqiang Wang
Journal:  Bioorg Med Chem Lett       Date:  2011-02-18       Impact factor: 2.823

9.  Design, Synthesis, and Biological Evaluations of Hydroxypyridonecarboxylic Acids as Inhibitors of HIV Reverse Transcriptase Associated RNase H.

Authors:  Jayakanth Kankanala; Karen A Kirby; Feng Liu; Lena Miller; Eva Nagy; Daniel J Wilson; Michael A Parniak; Stefan G Sarafianos; Zhengqiang Wang
Journal:  J Med Chem       Date:  2016-04-29       Impact factor: 7.446

10.  Inhibitors of HIV-1 Reverse Transcriptase-Associated Ribonuclease H Activity.

Authors:  Tatiana Ilina; Krystal Labarge; Stefan G Sarafianos; Rieko Ishima; Michael A Parniak
Journal:  Biology (Basel)       Date:  2012-10-19
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  9 in total

Review 1.  HBV replication inhibitors.

Authors:  Claire Pierra Rouviere; Cyril B Dousson; John E Tavis
Journal:  Antiviral Res       Date:  2020-05-05       Impact factor: 5.970

Review 2.  Chemical Approaches to Inhibiting the Hepatitis B Virus Ribonuclease H.

Authors:  John E Tavis; Grigoris Zoidis; Marvin J Meyers; Ryan P Murelli
Journal:  ACS Infect Dis       Date:  2018-03-22       Impact factor: 5.084

3.  Shedding light on RNaseH: a promising target for hepatitis B virus (HBV).

Authors:  Tiffany C Edwards; Nathan L Ponzar; John E Tavis
Journal:  Expert Opin Ther Targets       Date:  2019-05-22       Impact factor: 6.902

4.  4,5-Dihydroxypyrimidine Methyl Carboxylates, Carboxylic Acids, and Carboxamides as Inhibitors of Human Cytomegalovirus pUL89 Endonuclease.

Authors:  Tianyu He; Tiffany C Edwards; Jiashu Xie; Hideki Aihara; Robert J Geraghty; Zhengqiang Wang
Journal:  J Med Chem       Date:  2022-04-04       Impact factor: 8.039

5.  Cutting into the Substrate Dominance: Pharmacophore and Structure-Based Approaches toward Inhibiting Human Immunodeficiency Virus Reverse Transcriptase-Associated Ribonuclease H.

Authors:  Lei Wang; Stefan G Sarafianos; Zhengqiang Wang
Journal:  Acc Chem Res       Date:  2019-12-27       Impact factor: 22.384

6.  Amide-containing α-hydroxytropolones as inhibitors of hepatitis B virus replication.

Authors:  Qilan Li; Elena Lomonosova; Maureen J Donlin; Feng Cao; Austin O'Dea; Brienna Milleson; Alex J Berkowitz; John-Charles Baucom; John P Stasiak; Daniel V Schiavone; Rudolf G Abdelmessih; Anastasiya Lyubimova; Americo J Fraboni; Lauren P Bejcek; Juan A Villa; Emilio Gallicchio; Ryan P Murelli; John E Tavis
Journal:  Antiviral Res       Date:  2020-03-23       Impact factor: 5.970

7.  Effects of Moloney Leukemia Virus 10 Protein on Hepatitis B Virus Infection and Viral Replication.

Authors:  Maritza N Puray-Chavez; Mahmoud H Farghali; Vincent Yapo; Andrew D Huber; Dandan Liu; Tanyaradzwa P Ndongwe; Mary C Casey; Thomas G Laughlin; Mark Hannink; Philip R Tedbury; Stefan G Sarafianos
Journal:  Viruses       Date:  2019-07-17       Impact factor: 5.048

8.  8-Hydroxy-1,6-naphthyridine-7-carboxamides as Inhibitors of Human Cytomegalovirus pUL89 Endonuclease.

Authors:  Eunkyung Jung; Ryuichi Majima; Tiffany C Edwards; Ruben Soto-Acosta; Robert J Geraghty; Zhengqiang Wang
Journal:  ChemMedChem       Date:  2022-08-10       Impact factor: 3.540

9.  Metal binding 6-arylthio-3-hydroxypyrimidine-2,4-diones inhibited human cytomegalovirus by targeting the pUL89 endonuclease of the terminase complex.

Authors:  Lei Wang; Tiffany C Edwards; Rajkumar Lalji Sahani; Jiashu Xie; Hideki Aihara; Robert J Geraghty; Zhengqiang Wang
Journal:  Eur J Med Chem       Date:  2021-06-12       Impact factor: 7.088
  9 in total

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