Literature DB >> 29984646

Focusing on the Influenza Virus Polymerase Complex: Recent Progress in Drug Discovery and Assay Development.

Jiantao Zhang1, Yanmei Hu1, Rami Musharrafieh2, Hang Yin3, Jun Wang1,4.   

Abstract

Influenza viruses are severe human pathogens that pose persistent threat to public health. Each year more people die of influenza virus infection than that of breast cancer. Due to the limited efficacy associated with current influenza vaccines, as well as emerging drug resistance from small molecule antiviral drugs, there is a clear need to develop new antivirals with novel mechanisms of action. The influenza virus polymerase complex has become a promising target for the development of the next-generation of antivirals for several reasons. Firstly, the influenza virus polymerase, which forms a heterotrimeric complex that consists of PA, PB1, and PB2 subunits, is highly conserved. Secondly, both individual polymerase subunit (PA, PB1, and PB2) and inter-subunit interactions (PA-PB1, PB1- PB2) represent promising drug targets. Lastly, growing insight into the structure and function of the polymerase complex has spearheaded the structure-guided design of new polymerase inhibitors. In this review, we highlight recent progress in drug discovery and assay development targeting the influenza virus polymerase complex and discuss their therapeutic potentials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Entities:  

Keywords:  Influenza; PA; PB1; PB2; polymerase; ribonucleoprotein.

Mesh:

Substances:

Year:  2019        PMID: 29984646      PMCID: PMC6426683          DOI: 10.2174/0929867325666180706112940

Source DB:  PubMed          Journal:  Curr Med Chem        ISSN: 0929-8673            Impact factor:   4.530


  9 in total

1.  Discovery of Influenza Polymerase PA-PB1 Interaction Inhibitors Using an In Vitro Split-Luciferase Complementation-Based Assay.

Authors:  Jiantao Zhang; Yanmei Hu; Nan Wu; Jun Wang
Journal:  ACS Chem Biol       Date:  2019-11-21       Impact factor: 5.100

2.  Discovery of M2 channel blockers targeting the drug-resistant double mutants M2-S31N/L26I and M2-S31N/V27A from the influenza A viruses.

Authors:  Rami Musharrafieh; Chunlong Ma; Jun Wang
Journal:  Eur J Pharm Sci       Date:  2019-11-05       Impact factor: 4.384

3.  Investigating Different Mechanisms of Action in Combination Therapy for Influenza.

Authors:  Kelli Melville; Thalia Rodriguez; Hana M Dobrovolny
Journal:  Front Pharmacol       Date:  2018-10-23       Impact factor: 5.810

4.  Structural snapshots of actively transcribing influenza polymerase.

Authors:  Tomas Kouba; Petra Drncová; Stephen Cusack
Journal:  Nat Struct Mol Biol       Date:  2019-06-03       Impact factor: 15.369

5.  Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase.

Authors:  Serena Massari; Chiara Bertagnin; Maria Chiara Pismataro; Anna Donnadio; Giulio Nannetti; Tommaso Felicetti; Stefano Di Bona; Maria Giulia Nizi; Leonardo Tensi; Giuseppe Manfroni; Maria Isabel Loza; Stefano Sabatini; Violetta Cecchetti; Jose Brea; Laura Goracci; Arianna Loregian; Oriana Tabarrini
Journal:  Eur J Med Chem       Date:  2020-10-16       Impact factor: 6.514

6.  A computational framework of host-based drug repositioning for broad-spectrum antivirals against RNA viruses.

Authors:  Zexu Li; Yingjia Yao; Xiaolong Cheng; Qing Chen; Wenchang Zhao; Shixin Ma; Zihan Li; Hu Zhou; Wei Li; Teng Fei
Journal:  iScience       Date:  2021-02-05

7.  A Herbal Mixture Formula of OCD20015-V009 Prophylactic Administration to Enhance Interferon-Mediated Antiviral Activity Against Influenza A Virus.

Authors:  Eun-Bin Kwon; You-Chang Oh; Youn-Hwan Hwang; Wei Li; Seok-Man Park; Ryong Kong; Young Soo Kim; Jang-Gi Choi
Journal:  Front Pharmacol       Date:  2021-11-24       Impact factor: 5.810

Review 8.  Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins.

Authors:  Lingxin Hou; Ying Zhang; Han Ju; Srinivasulu Cherukupalli; Ruifang Jia; Jian Zhang; Bing Huang; Arianna Loregian; Xinyong Liu; Peng Zhan
Journal:  Acta Pharm Sin B       Date:  2021-11-19       Impact factor: 14.903

9.  In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses.

Authors:  Liva Checkmahomed; Blandine Padey; Andrés Pizzorno; Olivier Terrier; Manuel Rosa-Calatrava; Yacine Abed; Mariana Baz; Guy Boivin
Journal:  Viruses       Date:  2020-10-08       Impact factor: 5.048

  9 in total

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