tetano
Editor, Senior Moderator
Viruses. 2019 Sep 5;11(9). pii: E826. doi: 10.3390/v11090826.
[h=1]A Parallel Phenotypic Versus Target-Based Screening Strategy for RNA-Dependent RNA Polymerase Inhibitors of the Influenza A Virus.[/h] Zhao X[SUP]1[/SUP], Wang Y[SUP]2[/SUP], Cui Q[SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Li P[SUP]6[/SUP], Wang L[SUP]7[/SUP], Chen Z[SUP]8[/SUP], Rong L[SUP]9[/SUP], Du R[SUP]10,[/SUP][SUP]11,[/SUP][SUP]12[/SUP].
[h=3]Author information[/h] 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.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Influenza A virus; RNA dependent RNA polymerase inhibitor; phenotypic screen; target-based screen
PMID: 31491939 DOI: 10.3390/v11090826
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[h=1]A Parallel Phenotypic Versus Target-Based Screening Strategy for RNA-Dependent RNA Polymerase Inhibitors of the Influenza A Virus.[/h] Zhao X[SUP]1[/SUP], Wang Y[SUP]2[/SUP], Cui Q[SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Li P[SUP]6[/SUP], Wang L[SUP]7[/SUP], Chen Z[SUP]8[/SUP], Rong L[SUP]9[/SUP], Du R[SUP]10,[/SUP][SUP]11,[/SUP][SUP]12[/SUP].
[h=3]Author information[/h] 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.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Influenza A virus; RNA dependent RNA polymerase inhibitor; phenotypic screen; target-based screen
PMID: 31491939 DOI: 10.3390/v11090826
Free full text