2. Academic Validation
  3. A Parallel Phenotypic Versus Target-Based Screening Strategy for RNA-Dependent RNA Polymerase Inhibitors of the Influenza A Virus

A Parallel Phenotypic Versus Target-Based Screening Strategy for RNA-Dependent RNA Polymerase Inhibitors of the Influenza A Virus

  • Viruses. 2019 Sep 5;11(9):826. doi: 10.3390/v11090826.
Xiujuan Zhao 1,  Yanyan Wang 2,  Qinghua Cui 3 4 5,  Ping Li 6,  Lin Wang 7,  Zinuo Chen 8,  Lijun Rong 9,  Ruikun Du 10 11 12
Affiliations

Affiliations

  • 1 College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. xiujuan95@163.com.
  • 2 College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
  • 3 College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. cuiqinghua1122@163.com.
  • 4 Shandong Provincial Collaborative Innovation Center for Antiviral Traditional Chinese Medicine, Jinan 250355, China. cuiqinghua1122@163.com.
  • 5 Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao 266122, China. cuiqinghua1122@163.com.
  • 6 College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. liping9309@163.com.
  • 7 College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. lynn942@163.com.
  • 8 College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. chenzinuo96@163.com.
  • 9 Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA. lijun@uic.edu.
  • 10 College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. duzi857@163.com.
  • 11 Shandong Provincial Collaborative Innovation Center for Antiviral Traditional Chinese Medicine, Jinan 250355, China. duzi857@163.com.
  • 12 Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao 266122, China. duzi857@163.com.
PMID: 31491939 DOI: 10.3390/v11090826
Abstract

Influenza A virus infections cause significant morbidity and mortality, and novel antivirals are urgently needed. Influenza RNA-dependent RNA polymerase (RdRp) activity has been acknowledged as a promising target for novel antivirals. In this study, a phenotypic versus target-based screening strategy was established to identify the influenza A virus inhibitors targeting the virus RNA transcription/replication steps by sequentially using an RdRp-targeted screen and a replication-competent reporter virus-based approach using the same compounds. To demonstrate the utility of this approach, a pilot screen of a library of 891 compounds derived from Natural Products was carried out. Quality control analysis indicates that the primary screen was robust for identification of influenza A virus inhibitors targeting RdRp activity. Finally, two hit candidates were identified, and one was validated as a putative RdRp inhibitor. This strategy can greatly reduce the number of false positives and improve the accuracy and efficacy of primary screening, thereby providing a powerful tool for Antiviral discovery.

Keywords

Influenza A virus; RNA dependent RNA polymerase inhibitor; phenotypic screen; target-based screen.

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