ArticleJournal of computer-aided molecular design2010
Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease.
Article in Journal of computer-aided molecular design, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 36 citations in OpenAlex.
- Antiviral and antimicrobial applications of chalcones and their derivatives: From nature to greener synthesis.Heliyon · 2023Review
- Structure-Based Design and Pharmacophore-Based Virtual Screening of Combinatorial Library of Triclosan Analogues Active against Enoyl-Acyl Carrier Protein Reductase ofInternational journal of molecular sciences · 2023Article
- Advances in Computational Methods to Discover New NS2B-NS3 Inhibitors Useful Against Dengue and Zika Viruses.Current topics in medicinal chemistry · 2022Review
- Antiviral agents against COVID-19: structure-based design of specific peptidomimetic inhibitors of SARS-CoV-2 main protease.RSC advances · 2020Article
- Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling.PloS one · 2019Article
- How accurate is the description of ligand-protein interactions by a hybrid QM/MM approach?Journal of molecular modeling · 2017Article
- Enhanced QSAR model performance by integrating structural and gene expression information.Molecules (Basel, Switzerland) · 2013Article
- New binding site conformations of the dengue virus NS3 protease accessed by molecular dynamics simulation.PloS one · 2013Article
- High content screening of a kinase-focused library reveals compounds broadly-active against dengue viruses.PLoS neglected tropical diseases · 2013Article
- Computer-assisted combinatorial design of bicyclic thymidine analogs as inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.Journal of computer-aided molecular design · 2011Article
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Authors and funding
2 authors at 1 institution in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serine protease activity of the NS3 protein of Dengue virus is an important target of antiviral agents that interfere with the viral polyprotein precursor processing catalyzed by the NS3 protease (NS3pro), which is important for the viral replication and maturation. Recent studies showed that substrate-based peptidomimetics carrying an electrophilic warhead inhibit the NS2B-NS3pro cofactor-protease complex with inhibition constants in the low micromolar concentration range when basic amino acid residues occupy P(1) and P(2) positions of the inhibitor, and an aldehyde warhead is attached to the P(1). We have used computer-assisted combinatorial techniques to design, focus using the NS2B-NS3pro receptor 3D structure, and in silico screen a virtual library of more than 9,200 peptidomimetic analogs targeted around the template inhibitor Bz-Nle-Lys-Arg-Arg-H (Bz-benzoyl) that are composed mainly of unusual amino acid residues in all positions P(1)-P(4). The most promising virtual hits were analyzed in terms of computed enzyme-inhibitor interactions and Adsorption, Distribution, Metabolism and Excretion (ADME) related physico-chemical properties. Our study can direct the interest of medicinal chemists working on a next generation of antiviral chemotherapeutics against the Dengue Fever towards the explored subset of the chemical space that is predicted to contain peptide aldehydes with NS3pro inhibition potencies in nanomolar range which display ADME-related properties comparable to the training set inhibitors.
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