Development and validation of a high-throughput screen for inhibitors of SARS CoV and its application in screening of a 100,000-compound library

Journal of Biomolecular Screening
William E SeversonColleen B Jonsson


The authors have developed a high-throughput screen (HTS) that allows for the identification of potential inhibitors of the severe acute respiratory syndrome coronavirus (SARS CoV) from large compound libraries. The luminescent-based assay measures the inhibition of SARS CoV-induced cytopathic effect (CPE) in Vero E6 cells. The assay was validated in 96-well plates in a BSL3 containment facility. The assay is sensitive and robust, with Z values > 0.6, signal to background (S/B) > 16, and signal to noise (S/N) > 3. The assay was further validated with 2 different diversity sets of compounds against the SARS CoV. The "hit" rate for both libraries was approximately 0.01%. The validated HTS assay was then employed to screen a 100,000-compound library against SARS CoV. The hit rate for the library in a single-dose format was determined to be approximately 0.8%. Screening of the 3 libraries resulted in the identification of several novel compounds that effectively inhibited the CPE of SARS CoV in vitro-compounds which will serve as excellent lead candidates for further evaluation. At a 10-microM concentration, 3 compounds with selective indexes (SI50) of > 53 were discovered.


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Apr 3, 2003·The New England Journal of Medicine·Kenneth W TsangKar N Lai
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Nov 6, 2010·Assay and Drug Development Technologies·Lynn RasmussenE Lucile White
Sep 25, 2008·Journal of Biomolecular Screening·William E SeversonColleen B Jonsson
Apr 17, 2014·Assay and Drug Development Technologies·Bersabeh TigabuJames W Noah
Jun 1, 2008·Expert Opinion on Drug Discovery·Neil GreenHong Fang
Jun 1, 2008·Expert Opinion on Drug Discovery·Andrew L NilesTerry L Riss
Feb 25, 2015·Assay and Drug Development Technologies·Lynn RasmussenJames W Noah
Jan 24, 2014·Drug Discovery Today. Technologies·David W Sheppard, Jacqueline A MacRitchie
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Mar 9, 2019·Expert Opinion on Drug Discovery·Allison L Totura, Sina Bavari
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Feb 25, 2021·Nature Biotechnology·Ruili HuangWei Zheng
Dec 22, 2020·ACS Infectious Diseases·Kirill GorshkovWei Zheng
Aug 21, 2021·Frontiers in Medicine·Brittany A ComunaleQiyi Xie
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