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 HCV antiviral drugs and their structural analogues – several of them 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 thirteen such antiviral 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, relatively higher electrophilicity index, aromatic rings and heteroatoms that participate in hydrogen bonding. Among the drugs tested, four compounds 10-13 showed excellent results – binding affinities -11.2 to -11.5 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.

Version notes

Same as Version 4. The only difference is a few changes in the online version of the abstract (removal of html characters present in the online version of the abstract).


Thumbnail image of In Silico Drug Repurposing for coronavirus (COVID-19) Screening known HCV drugs against the SARS-CoV-2 Spike protein (6M0J) K. G. Kalamatianos_260221_v4.pdf

Supplementary material

Thumbnail image of compounds_of_Table2_smiles.csv
SMILES of compounds in Table 2
Thumbnail image of structures_results_project2_19042021_submit.xlsx
Table of docking trials and results