Molecular docking of porphyrin-like complexes to SARS-CoV-2 main protease

Abstract

Molecular docking method, which was recently modified to allow traditional and covalent docking of organometallic compounds [1], was used to theoretically investigate the potential binding of 15 copper(II) complexes with porphyrin-like ligands to main protease of SARS-CoV-2 virion (CLpro). Method was implemented by importing published parameters into the program GOLD from the CCDC package. Target of the docking experiments was active site of the CLpro. Method was validated by redocking of N3 inhibitor, and by comparing obtained results with published crystal structure [2]. Structures of investigated complexes were obtained by filtering Cambridge Structural Database for porphyrin-like compounds with copper(II) ion. Each structure was refined using semi-empirical PM6 method implemented in MOPAC 2016 and subsequently modified for docking experiments with dummy hydrogen atoms that simulate metallic d-orbitals. Docking experiments were performed with 50 genetic algorithm runs for each investigated complex, GoldScore function was used to score fitness, no early termination was set, and rest of the settings were left at the default values. Obtained scores were then compared to the scores derived from experiment with known inhibitor to rank inhibitory potential of investigated compounds.