Discovery of novel inhibitors against main protease (Mpro) of SARS-CoV-2 via virtual screening and biochemical evaluation

Autor:	Zhili Zuo, Li Zhang, Yu Lei, Bin Liu, Hang Xie, Yechun Xu, Sheng Guo
Rok vydání:	2020
Předmět:	3CLpro 3C-like protease medicine.medical_treatment Drug Evaluation Preclinical 01 natural sciences Biochemistry MERS-CoV middle east respiratory syndrome coronavirus Docking (dog) PLP papain-like proteases PAINS pan assay interference compounds Drug Discovery BBB blood brain barrier penetration PDB protein data bank Pathogen RMSD root mean square difference Coronavirus 3C Proteases media_common ORF open reading frame genes HCoV-229E Human coronavirus 229E Chemistry HIA human intestinal absorption COVID-19 corona virus disease 2019 N Nucleocapsid protein Molecular Docking Simulation DS 4.0 Discovery Studio 4.0 Biochemical evaluation Virtual screening Drug 2019-20 coronavirus outbreak Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) media_common.quotation_subject HCoV-NL63 Human coronavirus NL63 Computational biology SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 Antiviral Agents Article ER endoplasmic reticulum E envelope protein HCoV-OC43 Human coronavirus OC43 medicine Humans UTR untranslated regions Protease Inhibitors Molecular Biology ComputingMethodologies_COMPUTERGRAPHICS nsps non-structural proteins Protease pp1ab polyprotein 1ab S spike glycoprotein 010405 organic chemistry SARS-CoV-2 pp1a polyprotein 1a Organic Chemistry 0104 chemical sciences Mpro main protease 010404 medicinal & biomolecular chemistry M membrane protein Main protease IC50 Half maximal inhibitory concentration HCoV-HKU1 Human coronavirus Hong Kong University 1 CYP450 cytochrome P450
Zdroj:	Bioorganic Chemistry
ISSN:	1090-2120
Popis:	Graphical abstract SARS-CoV-2 is the pathogen that caused the global COVID-19 outbreak in 2020. Promising progress has been made in developing vaccines and antiviral drugs. Antivirals medicines are necessary complements of vaccines for post-infection treatment. The main protease (Mpro) is an extremely important protease in the reproduction process of coronaviruses which cleaves pp1ab over more than 11 cleavage sites. In this work, two active main protease inhibitors were found via docking-based virtual screening and bioassay. The IC50 of compound VS10 was 0.20 μM, and the IC50 of compound VS12 was 1.89 μM. The finding in this work can be helpful to understand the interactions of main protease and inhibitors. The active candidates could be potential lead compounds for future drug design.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::64603f79f7dca1b2529aabbb2a2d9f48 https://pubmed.ncbi.nlm.nih.gov/33667900 Zobrazit plný text záznamu Full Text from ScienceDirect