High-throughput virtual screening of drug databanks for potential inhibitors of SARS-CoV-2 spike glycoprotein

Ibrahim E. Awad, Abd Al-Aziz A. Abu-Saleh, Sweta Sharma, Arpita Yadav, Raymond A. Poirier

10.1080/07391102.2020.1835721

Research curated

Abstract

COVID-19, which is caused by a novel coronavirus known as SARS-CoV-2, has spread rapidly around the world, and it has infected more than 29 million individuals as recorded on 16 September 2020. Much effort has been made to stop the virus from spreading, and there are currently no approved pharmaceutical products to treat COVID-19. Here, we apply an in silico approach to investigate more than 3800 FDA approved drugs on the viral RBD S1-ACE2 interface as a target. The compounds were investigated through flexible ligand docking, ADME property calculations and protein–ligand interaction maps. Molecular dynamics (MD) simulations were also performed on eleven compounds to study the stability and the interactions of the protein–ligand complexes. The MD simulations show that bagrosin, chidamide, ebastine, indacaterol, regorafenib, salazosulfadimidine, silodosin and tasosartan are relatively stable near the C terminal domain (CTD1) of the S1 subunit of the viral S protein. The relative MMGBSA binding energies show that silodosin has the best binding to the target. The constant velocity steered molecular dynamics (SMD) simulations show that silodosin preferentially interacts with the RBD S1 and has potential to act as an interfering compound between viral spike–host ACE2 interactions.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Bagrosin	5-Methyl-5-(3-phenanthryl)hydantoin
Chidamide
Ebastine
indacaterol
salazosulfadimidine
Silodosin
Tasosartan
Angiotensin-converting enzyme 2-Spike glycoprotein interface
regorafenib

Related interactions

Target	Drug	Type	Result
Angiotensin-converting enzyme 2-Spike glycoprotein interface	Bagrosin	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	Chidamide	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	indacaterol	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	regorafenib	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	salazosulfadimidine	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	Silodosin	Computational	positive
Angiotensin-converting enzyme 2-Spike glycoprotein interface	Tasosartan	Computational	positive