In Silico Identification of Potential Inhibitors of the SARS-CoV-2 Main Protease among a PubChem Database of Avian Infectious Bronchitis Virus 3CLPro Inhibitors

Remarkable structural homologies between the main proteases of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the avian infectious bronchitis virus (IBV) were revealed by comparative amino-acid sequence and 3D structural alignment. Assessing whether reported IBV 3CLPro inhibitors could also interact with SARS-CoV-2 has been undertaken in silico using a PubChem BioAssay database of 388 compounds active on the avian infectious bronchitis virus 3C-like protease. Docking studies of this database on the SARS-CoV-2 protease resulted in the identification of four covalent inhibitors targeting the catalytic cysteine residue and five non-covalent inhibitors for which the binding was further investigated by molecular dynamics (MD) simulations. Predictive ADMET calculations on the nine compounds suggest promising pharmacokinetic properties.

Automated summary

Comparative analysis of amino acid sequences and 3D structural alignment revealed significant structural homologies between the main proteases of SARS-CoV-2 and IBV. In silico screening using a PubChem BioAssay database identified four covalent inhibitors and five non-covalent inhibitors for SARS-CoV-2 protease. Molecular dynamics simulations further investigated the binding of these inhibitors, and predictive ADMET calculations suggested promising pharmacokinetic properties for the nine compounds.