High-throughput screening of a 100,000-compound library for inhibitors of influenza a virus (H3N2)

William E. Severson, Michael McDowell, Subramaniam Ananthan, Dong Hoon Chung, Lynn Rasmussen, Melinda I. Sosa, E. Lucile White, James Noah, Colleen Jonsson

Research output: Contribution to journalArticle

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Abstract

Using a highly reproducible and robust cell-based high-throughput screening (HTS) assay, the authors screened a 100,000-compound 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.

Original languageEnglish (US)
Pages (from-to)879-887
Number of pages9
JournalJournal of Biomolecular Screening
Volume13
Issue number9
DOIs
StatePublished - Oct 1 2008

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Orthomyxoviridae
Viruses
Human Influenza
Libraries
Antiviral Agents
Screening
Viral Cytopathogenic Effect
Throughput
High-Throughput Screening Assays
Sulfonamides
Life Cycle Stages
Toxicity
Life cycle
Assays
Experiments
Molecules

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

High-throughput screening of a 100,000-compound library for inhibitors of influenza a virus (H3N2). / Severson, William E.; McDowell, Michael; Ananthan, Subramaniam; Chung, Dong Hoon; Rasmussen, Lynn; Sosa, Melinda I.; White, E. Lucile; Noah, James; Jonsson, Colleen.

In: Journal of Biomolecular Screening, Vol. 13, No. 9, 01.10.2008, p. 879-887.

Research output: Contribution to journalArticle

Severson, WE, McDowell, M, Ananthan, S, Chung, DH, Rasmussen, L, Sosa, MI, White, EL, Noah, J & Jonsson, C 2008, 'High-throughput screening of a 100,000-compound library for inhibitors of influenza a virus (H3N2)', Journal of Biomolecular Screening, vol. 13, no. 9, pp. 879-887. https://doi.org/10.1177/1087057108323123
Severson, William E. ; McDowell, Michael ; Ananthan, Subramaniam ; Chung, Dong Hoon ; Rasmussen, Lynn ; Sosa, Melinda I. ; White, E. Lucile ; Noah, James ; Jonsson, Colleen. / High-throughput screening of a 100,000-compound library for inhibitors of influenza a virus (H3N2). In: Journal of Biomolecular Screening. 2008 ; Vol. 13, No. 9. pp. 879-887.
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