Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease.

M. Tsuji

10.1002/2211-5463.12875

Research curated

Abstract

A novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2], or 2019 novel coronavirus [2019‐nCoV]) has been identified as the pathogen of coronavirus disease 2019 (COVID‐19). The main protease (Mpro, also called 3‐chymotrypsin‐like protease [3CLpro]) of SARS‐CoV‐2 is a potential target for treatment of COVID‐19. A Mpro homodimer structure suitable for docking simulations was prepared using a crystal structure (PDB ID: 6Y2G; resolution 2.20 Å). Structural refinement was performed in the presence of peptidomimetic α‐ketoamide inhibitors, which were previously disconnected from each Cys145 of the Mpro homodimer, and energy calculations were performed. Structure‐based virtual screenings were performed using the ChEMBL database. Through a total of 1,485,144 screenings, 64 potential drugs (11 approved, 14 clinical, and 39 preclinical drugs) were predicted to show high binding affinity with Mpro. Additional docking simulations for predicted compounds with high binding affinity with Mpro suggested that 28 bioactive compounds may have potential as effective anti‐SARS‐CoV‐2 drug candidates. The procedure used in this study is a possible strategy for discovering anti‐SARS‐CoV‐2 drugs from drug libraries that may significantly shorten the clinical development period with regard to drug repositioning.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Lobendazole	6306-71-4, Ethyl 1H-benzimidazol-2-ylcarbamate, Ethyl 2-benzimidazolecarbamate, 2-Carboethoxyaminobenzimidazole
Sulfamethizole
Sulfathiazole
Kanamycin A	Kanamycin
Phthalylsulfathiazole
Sulfamoxole
Sulfaethidole
Sulfametrole
Pentisomicin	Pentisomicin, 5-Episisomicin, Mutamicin 6, Mutamycin 6, 5-epi-Sisomicin
Sanfetrinem cilexetil
Glybuthiazol	Glipasol, Glypasol, GLYBUTHIAZOLE, Glybuthizolum
Benaxibine	27661-27-4, Benaxibina, Benaxibinum
Glybuzole
Acefluranol	BX-591
Tanzisertib
Viprostol	Dhv-PGE2Me, UNII-O2Y6I4Y8TF, O2Y6I4Y8TF, 73647-73-1
Maleylsulfathiazole	UNII-N7T6304257, 515-57-1, Maleylsulfathiazol, 4'-(2-Thiazolylsulfamoyl)maleanilic acid
Ramifenazone	3615-24-5, Isopyrin, Isopirina, Isopyrine
Betamicin	Betamicin sulfate, UNII-FO90AO023F, FO90AO023F
Phthalylsulfamethizole
Setileuton	910656-27-8, MK-0633, UNII-0U2750935P, 0U2750935P
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Tobramycin	Tobrex, Tobi

Related interactions

Target	Drug	Type	Result
3C-like protease	Lobendazole	Computational	positive
3C-like protease	Sulfamethizole	Computational	positive
3C-like protease	Sulfathiazole	Computational	positive
3C-like protease	Kanamycin A	Computational	positive
3C-like protease	Phthalylsulfathiazole	Computational	positive
3C-like protease	Sulfamoxole	Computational	positive
3C-like protease	Sulfaethidole	Computational	positive
3C-like protease	Sulfametrole	Computational	positive
3C-like protease	Pentisomicin	Computational	positive
3C-like protease	Betamicin	Computational	positive
3C-like protease	Sanfetrinem cilexetil	Computational	positive
3C-like protease	Glybuthiazol	Computational	positive
3C-like protease	Acefluranol	Computational	positive
3C-like protease	Tanzisertib	Computational	positive
3C-like protease	Viprostol	Computational	positive
3C-like protease	Phthalylsulfamethizole	Computational	positive
3C-like protease	Maleylsulfathiazole	Computational	positive
3C-like protease	Ramifenazone	Computational	positive
3C-like protease	Setileuton	Computational	positive
3C-like protease	Tobramycin	Computational	positive