In Silico Identification of Potential Inhibitors of the SARS-CoV-2 Main Protease among a PubChem Database of Avian Infectious Bronchitis Virus 3CLPro Inhibitors.
Laurent SoulèreThibaut BarbierYves QueneauPublished in: Biomolecules (2023)
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.
Keyphrases
- sars cov
- molecular dynamics
- respiratory syndrome coronavirus
- density functional theory
- amino acid
- molecular docking
- disease virus
- coronavirus disease
- adverse drug
- emergency department
- molecular dynamics simulations
- cancer therapy
- climate change
- drug delivery
- fluorescent probe
- small molecule
- monte carlo
- human health
- dna binding
- electronic health record
- crystal structure