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)

Authors

Abstract

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 correspond-ing binding affinities of thirteen such antiretroviral com-pounds 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.

Version notes

E3/03-03-2021 E2/21-12-2020 E1/24-08-2020

Content

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_v3.pdf