ArticleBMC structural biology2015
Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: homology modelling and molecular dynamic studies.
Article in BMC structural biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Repurposing the Open Global Health Library for the discovery of novel Mpro destabilizers with scope as broad-spectrum antivirals.Frontiers in pharmacology · 2024Article
- Development of Masitinib Derivatives with Enhanced MMolecules (Basel, Switzerland) · 2023Article
- Discovery of 3CLpro inhibitor of SARS-CoV-2 main protease.Future science OA · 2023Article
- Repurposing dyphylline as a pan-coronavirus antiviral therapy.Future medicinal chemistry · 2022Article
- Peptide candidates for the development of therapeutics and vaccines against β-coronavirus infection.Bioengineered · 2022Review
- Inhibitors of Coronavirus 3CL Proteases Protect Cells from Protease-Mediated Cytotoxicity.Journal of virology · 2021Article
- Targeting novel structural and functional features of coronavirus protease nsp5 (3CLThe Journal of general virology · 2021Review
- Novel Small-Molecule Scaffolds as Candidates against the SARS Coronavirus 2 Main Protease: A Fragment-Guided in Silico Approach.Molecules (Basel, Switzerland) · 2020Article
- A simplified cell-based assay to identify coronavirus 3CL protease inhibitors.bioRxiv : the preprint server for biology · 2020Article
- A Potential Peptide From Soy Cheese Produced UsingFrontiers in molecular biosciences · 2020Article
- Viral Emerging Diseases: Challenges in Developing Vaccination Strategies.Frontiers in immunology · 2020Review
- Review
- Potential Broad Spectrum Inhibitors of the Coronavirus 3CLpro: A Virtual Screening and Structure-Based Drug Design Study.Viruses · 2015Article
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3 authors.
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Abstract
backgroundThe coronavirus 3 chymotrypsin-like protease (3CL(pro)) is a validated target in the design of potential anticoronavirus inhibitors. The high degree of homology within the protease's active site and substrate conservation supports the identification of broad spectrum lead compounds. A previous study identified the compound ML188, also termed 16R, as an inhibitor of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) 3CL(pro). This study will detail the generation of a homology model of the 3CL(pro) of the human coronavirus OC43 and determine the potential of 16R to form a broad-spectrum lead compound. MODELLER was used to generate a suitable three-dimensional model of the OC43 3CL(pro) and the Prime module of Schrӧdinger predicted the binding conformation and free energy of binding of 16R within the 3CL(pro) active site. Molecular dynamics further confirmed ligand stability and hydrogen bonding networks.
resultsA high quality homology model of the OC43 3CL(pro) was successfully generated in an active conformation. Further studies reproduced the binding pose of 16R within the active site of the generated model, where its free energy of binding was shown to equal that of the 3CL(pro) of SARS-CoV, a receptor it is experimentally proven to inhibit. The stability of the ligand was subsequently confirmed by molecular dynamics.
conclusionThe lead compound 16R may represent a broad-spectrum inhibitor of the 3CL(pro) of OC43 and potentially other coronaviruses. This study provides an atomistic structure of the 3CL(pro) of OC43 and supports further experimental validation of the inhibitory effects of 16R. These findings further confirm that the 3CL(pro) of coronaviruses can be inhibited by broad spectrum lead compounds.
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