ArticleChemical biology & drug design2008
Development of broad-spectrum halomethyl ketone inhibitors against coronavirus main protease 3CL(pro).
Article in Chemical biology & drug design, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Covalent inhibition of New Delhi metallo-β-lactamases NDM-1 and NDM-5 by 3-bromopyruvate.JAC-antimicrobial resistance · 2026Article
- Discovery of an autoinhibited conformation in mesotrypsin reveals a strategy for selective serine protease inhibition.Science advances · 2025Article
- Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review.European journal of medicinal chemistry · 2023Review
- Design of SARS-CoV-2 Mpro, PLpro dual-target inhibitors based on deep reinforcement learning and virtual screening.Future medicinal chemistry · 2022Article
- Perspectives on SARS-CoV-2 Main Protease Inhibitors.Journal of medicinal chemistry · 2021Review
- Multi-omics data integration and network-based analysis drives a multiplex drug repurposing approach to a shortlist of candidate drugs against COVID-19.Briefings in bioinformatics · 2021Article
- Dimethyl sulfoxide reduces the stability but enhances catalytic activity of the main SARS-CoV-2 protease 3CLpro.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Targeting novel structural and functional features of coronavirus protease nsp5 (3CLThe Journal of general virology · 2021Review
- Protein structural heterogeneity: A hypothesis for the basis of proteolytic recognition by the main protease of SARS-CoV and SARS-CoV-2.Biochimie · 2021Article
- Evaluation of certain medicinal plants compounds as new potential inhibitors of novel corona virus (COVID-19) using molecular docking analysis.In silico pharmacology · 2021Article
- Genomics functional analysis and drug screening of SARS-CoV-2.Genes & diseases · 2020Article
- Unveiling the molecular mechanism of SARS-CoV-2 main protease inhibition from 137 crystal structures using algebraic topology and deep learning.Chemical science · 2020Article
- Peptidyl Fluoromethyl Ketones and Their Applications in Medicinal Chemistry.Molecules (Basel, Switzerland) · 2020Review
- SARS-CoV and SARS-CoV-2 main protease residue interaction networks change when bound to inhibitor N3.Journal of structural biology · 2020Article
- Design and Evaluation of Anti-SARS-Coronavirus Agents Based on Molecular Interactions with the Viral Protease.Molecules (Basel, Switzerland) · 2020Review
- Progress in Developing Inhibitors of SARS-CoV-2 3C-Like Protease.Microorganisms · 2020Review
- Repositioning of 8565 Existing Drugs for COVID-19.The journal of physical chemistry letters · 2020Article
- Structural Basis for Inhibiting Porcine Epidemic Diarrhea Virus Replication with the 3C-Like Protease Inhibitor GC376.Viruses · 2020Article
- Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine.Antiviral research · 2018Article
- Broad-spectrum inhibitors against 3C-like proteases of feline coronaviruses and feline caliciviruses.Journal of virology · 2015Article
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Authors and funding
6 authors.
Funding
Abstract
Coronaviruses comprise a large group of RNA viruses with diverse host specificity. The emergence of highly pathogenic strains like the SARS coronavirus (SARS-CoV), and the discovery of two new coronaviruses, NL-63 and HKU1, corroborates the high rate of mutation and recombination that have enabled them to cross species barriers and infect novel hosts. For that reason, the development of broad-spectrum antivirals that are effective against several members of this family is highly desirable. This goal can be accomplished by designing inhibitors against a target, such as the main protease 3CL(pro) (M(pro)), which is highly conserved among all coronaviruses. Here 3CL(pro) derived from the SARS-CoV was used as the primary target to identify a new class of inhibitors containing a halomethyl ketone warhead. The compounds are highly potent against SARS 3CL(pro) with K(i)'s as low as 300 nM. The crystal structure of the complex of one of the compounds with 3CL(pro) indicates that this inhibitor forms a thioether linkage between the halomethyl carbon of the warhead and the catalytic Cys 145. Furthermore, Structure Activity Relationship (SAR) studies of these compounds have led to the identification of a pharmacophore that accurately defines the essential molecular features required for the high affinity.
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