Site mapping and small molecule blind docking reveal a possible target site on the SARS-CoV-2 main protease dimer interface.

Site mapping and small molecule blind docking reveal a possible target site on the SARS-CoV-2 main protease dimer interface. Comput Biol Chem. 2020 Sep 05;89:107372 Authors: Liang J, Karagiannis C, Pitsillou E, Darmawan KK, Ng K, Hung A, Karagiannis TC Abstract The SARS-CoV-2 virus is causing COVID-19 resulting in an ongoing pandemic with serious health, social, and economic implications. Much research is focused in repurposing or identifying new small molecules which may interact with viral or host-cell molecular targets. An important SARS-CoV-2 target is the main protease (Mpro), and the peptidomimetic α-ketoamides represent prototypical experimental inhibitors. The protease is characterised by the dimerization of two monomers each which contains the catalytic dyad defined by Cys145 and His41 residues (active site). Dimerization yields the functional homodimer. Here, our aim was to investigate small molecules, including lopinavir and ritonavir, α-ketoamide 13b, and ebselen, for their ability to interact with the Mpro. The sirtuin 1 agonist SRT1720 was also used in our analyses. Blind docking to each monomer individually indicated preferential binding of the ligands in the active site. Site-mapping of the dimeric protease indicated a highly reactive pocket in the dimerization region at the domain III apex. Blind docking consistently indicated a strong preference of ligand binding in domain III, away from the active site. Molecular...
Source: Computational Biology and Chemistry - Category: Bioinformatics Authors: Tags: Comput Biol Chem Source Type: research