Biological and Medicinal Chemistry

Drug Repurposing for Coronavirus (COVID-19): In Silico Screening of Known Drugs Against the SARS-CoV-2 Spike Protein Bound to Angiotensin Converting Enzyme 2 (ACE2) (6M0J)



In this study FDA approved antiviral drugs and lopinavir analogues in clinical trials were tested for their inhibitory properties towards the SARS-CoV-2 Spike protein bound to angiotensin converting enzyme 2 (ACE2) (6M0J) using a virtual screening approach and computational chemistry methods. The most stable structures and the corresponding binding affinities of seventeen such antiretroviral compounds were obtained. Frontier molecular orbital theory, global reactivity descriptors, molecular docking calculations and electrostatic potential (ESP) analysis were used to hypothesize the bioactivity of these drugs against 6M0J. It is found that increased affinity for the protein is shown by inhibitors with large compound volume, small charge separation, low electrophilicity, aromatic rings and heteroatoms that participate in hydrogen bonding. Amongst the drugs tested, four compounds, PubChem CID 492005, CID 486507, CID 3010249 and lopinavir showed excellent results – binding interactions -9.0 to -9.3 kcal.mol-1. These four top scoring compounds may act as lead compounds for further experimental validation, clinical trials and even for the development of more potent antiviral agents against the SARS-CoV-2.

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