Premium
Structure‐Based Design and Synthesis of Highly Potent SARS‐CoV 3CL Protease Inhibitors
Author(s) -
Shao YiMing,
Yang WenBin,
Peng HungPin,
Hsu MinFeng,
Tsai KengChang,
Kuo TunHsun,
Wang Andrew H.J.,
Liang PoHuang,
Lin ChunHung,
Yang AnSuei,
Wong ChiHuey
Publication year - 2007
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200700254
Subject(s) - covid-19 , protease , chemistry , virology , combinatorial chemistry , structure–activity relationship , computational biology , stereochemistry , enzyme , biology , biochemistry , medicine , in vitro , infectious disease (medical specialty) , disease , pathology , outbreak
In a successful example of lead optimization by computer modeling prediction , computational technology was used to optimize a lead inhibitor (TL‐3) of the SARS‐CoV 3CL protease. A novel C 2 ‐symmetric diol ( 1 ) was then designed and synthesized, and displayed higher affinity than the original lead compound by one order of magnitude in its inhibition constant (0.6→0.073 μ M ). We believe that this approach has provided a platform for further lead optimization.