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)

19 July 2021, Version 4
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

E4/18-07-2021



E3/03-03-2021
Molecular Dynamics Simulation has been added to E2/21-12-2020




E2/21-12-2020

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. Amongst 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.


E1/24-08-2020

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. 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.

Keywords

SARS CoV 2
SARS-CoV-2 Spike protein
6M0J
drug repurposing screens
in silico screening
FDA drugs
Global reactivity descriptors
molecular docking calculations
ESP analysis
bioactivity of drugs
lopinavir
lopinavir analogues
remdesivir
darunavir
binding free energy calculations
binding dissociation constants
binding affinities
computational drug screen
paritaprevir
Elbasvir
elbasvir analogues

Supplementary materials

Title
Description
Actions
Title
Compounds_Table2_smiles
Description
SMILES of compounds in Table 2
Actions
Title
docking_results
Description
Table of docking trials and results
Actions

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