Novel Probes from the MLSCN

Screening of over 66,000 compounds from the MLSMR by scientists at the PCMD for inhibitors of Cathepsin B resulted in the identification and characterization of an alternate substrate, SID 16952359 [29]. This study also describes issues relating to the nucleophilicity of dithiothreitol (DTT) and cysteine, reductants frequently used in HTS protocols, and the potential for reactivity with electrophilic sites of probe molecules. 

The development of quantitative high-throughput screening (qHTS) paradigms that provide concentration-response curves for large chemical libraries in a 

Researchers at SRMLSC recently developed a HTS that allowed the identification of potential inhibitors of the severe acute respiratory syndrome coronavirus (SARS CoV) from large compound libraries [34], The luminescent-based assay, which measured the inhibition of SARS CoV-induced cytopathic effects (CPE) in Vero E6 cells, was validated with two 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 three libraries resulted in the identification of several novel compounds that effectively inhibited the CPE of SARS CoV in vitro. Three hit compounds, shown below, were identified as promising lead candidates for further evaluation. 

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