Sunday, July 24, 2011
Grand Ballroom, 5th fl (Sheraton New Orleans)
The 3C-like protease (3CLpro) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Structure based virtual screening of 308,307 chemical compounds was performed using the computation tool Autodock 3.0.5 on a WISDOM Production Environment. The top 1468 ranked compounds with free binding energy ranging from -14.0 to -17.09 kcal.mol-1 were selected to check the hydrogen bond interaction with amino acid residues in the active site of 3CLpro. Fifty-three compounds from 35 main groups were tested in an in vitro assay for inhibition of 3CLpro expressed by Escherichia coli. Seven of the fifty-three compounds were selected; their IC50 ranged from 38.57 ± 2.41 to 101.38 ± 3.27 μM. Two strong 3CLpro inhibitors were further identified as competitive inhibitors of 3CLpro with Ki of 9.11 ± 1.6 and 9.93 ± 0.44 μM. Hydrophobic and hydrogen bond interactions with amino acid residues in the active site of 3CLpro of one compound were also identified.