Prioritization of potential drugs targeting the SARS-CoV-2 main protease

Yanjin Li, Yu Zhang, Yikai Han, Tengfei Zhang, Ranran Du

10.26434/chemrxiv.12629858.v1

Research curated

Abstract

Since its outbreak in 2019, the acute respiratory syndrome caused by SARS-Cov-2 has become a severe global threat to human. The lack of effective drugs strongly limits the therapeutic treatment against this pandemic disease. Here we employed a computational approach to prioritize potential inhibitors that directly target the core enzyme of SARS-Cov-2, the main protease, which is responsible for processing the viral RNA-translated polyprotein into functional proteins for viral replication. Based on a largescale screening of over 13, 000 drug-like molecules, we have identified the most potential drugs that may suffice drug repurposing for SARS-Cov-2. Importantly, the second top hit is Beclabuvir, a known replication inhibitor of hepatitis C virus (HCV), which is recently reported to inhibit SARS-Cov-2 as well. We also noted several neurotransmitter-related ligands among the top candidates, suggesting a novel molecular similarity between this respiratory syndrome and neural activities. Our approach not only provides a comprehensive list of prioritized drug candidates for SARS-Cov-2, but also reveals intriguing molecular patterns that are worth future explorations.

Source: ChemRxiv

Related molecules

Name	Synonyms	Genes
Phthalylsulfamethizole
Danicopan
Galicaftor
Petesicatib
Phthalocyanine
Ergotamine
Dihydroergotoxine
Beclabuvir
Tirilazad
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
N-1H-indazol-5-yl-2-(6-methylpyridin-2-yl)quinazolin-4-amine
Cepharanthine	CEP

Related interactions

Target	Drug	Type	Result
3C-like protease	Phthalocyanine	Computational	positive
3C-like protease	Danicopan	Computational	positive
3C-like protease	Dihydroergotoxine	Computational	positive
3C-like protease	Galicaftor	Computational	positive
3C-like protease	N-1H-indazol-5-yl-2-(6-methylpyridin-2-yl)quinazolin-4-amine	Computational	positive
3C-like protease	Petesicatib	Computational	positive
3C-like protease	Ergotamine	Computational	positive
3C-like protease	Cepharanthine	Computational	positive
3C-like protease	Beclabuvir	Computational	positive
3C-like protease	Tirilazad	Computational	positive