Structural basis for the development of SARS 3CL protease inhibitors from a peptide mimic to an aza-decaline scaffold.

ABSTRACT: Design of inhibitors against severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CL(pro) ) is a potentially important approach to fight against SARS. We have developed several synthetic inhibitors by structure-based drug design. In this report, we reveal two crystal structures of SARS 3CL(pro) complexed with two new inhibitors based on our previous work. These structures combined with six crystal structures complexed with a series of related ligands reported by us are collectively analyzed. To these eight complexes, the structural basis for inhibitor binding was analyzed by the COMBINE method, which is a chemometrical analysis optimized for the protein-ligand complex. The analysis revealed that the first two latent variables gave a cumulative contribution ratio of r(2)  =

SUBMITTER: Teruya K 

PROVIDER: S-EPMC7159131 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature