Identification and characterization of inhibitors of West Nile virus

Wadsworth Center, New York State Department of Health, Albany, NY, USA.
Antiviral research (Impact Factor: 3.94). 07/2009; 83(1):71-9. DOI: 10.1016/j.antiviral.2009.03.005
Source: PubMed


Although flaviviruses cause significant human diseases, no antiviral therapy is currently available for clinical treatment of these pathogens. To identify flavivirus inhibitors, we performed a high-throughput screening of compound libraries using cells containing luciferase-reporting replicon of West Nile viruses (WNV). Five novel small molecular inhibitors of WNV were identified from libraries containing 96,958 compounds. The inhibitors suppress epidemic strain of WNV in cell culture, with EC(50) (50% effective concentration) values of <10microM and TI (therapeutic index) values of >10. Viral titer reduction assays, using various flaviviruses and nonflaviviruses, showed that the compounds have distinct antiviral spectra. Mode-of-action analysis showed that the inhibitors block distinct steps of WNV replication: four compounds inhibit viral RNA syntheses, while the other compound suppresses both viral translation and RNA syntheses. Biochemical enzyme assays showed that two compounds selectively inhibit viral RNA-dependent RNA polymerase (RdRp), while another compound specifically inhibits both RdRp and methyltransferase. The identified compounds could potentially be developed for treatment of flavivirus infections.

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Available from: Pei-Yong Shi, Apr 17, 2014
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    • "Using a cell-based assay, Puig-Basagoiti et al. identified a compound that inhibited the WNV N7 MTase activity with an IC 50 of 54 μmol/L (Puig-Basagoiti et al., 2009). They also found that the compound inhibited the growth of various flaviviruses with an EC 50 (50% effective concentration) in the low micromolar range (Puig-Basagoiti et al., 2009). "
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