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High-Throughput Screening of a 100,000-Compound Library for Inhibitors of Influenza A Virus (H3N2)

^* To whom correspondence should be addressed. E-mail: severson{at}sri.org.

	Abstract

Using a highly reproducible and robust cell-based high-throughput screening (HTS) assay, the authors screened a 100,000compound library at 14- and 114-µM compound concentration against influenza strain A/Udorn/72 (H3N2). The "hit" rates (>50% inhibition of the viral cytopathic effect) from the 14- and 114-µM screens were 0.022% and 0.38%, respectively. The hits were evaluated for their antiviral activity, cell toxicity, and selectivity in dose-response experiments. The screen at the lower concentration yielded 3 compounds, which displayed moderate activity (SI₅₀ = 10-49). Intriguingly, the screen at the higher concentration revealed several additional hits. Two of these hits were highly active with an SI₅₀ > 50. Time of addition experiments revealed 1 compound that inhibited early and 4 other compounds that inhibited late in the virus life cycle, suggesting they affect entry and replication, respectively. The active compounds represent several different classes of molecules such as carboxanilides, 1-benzoyl-3-arylthioureas, sulfonamides, and benzothiazinones, which have not been previously identified as having antiviral/anti-influenza activity. (Journal of Biomolecular Screening XXXX:xx-xx)

First published on September 23, 2008, doi:10.1177/1087057108323123

Journal of Biomolecular Screening 2008;13:879.

A more recent version of this article appeared on October 1, 2008


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