title: Searching for anthranilic acid-based thumb pocket 2 HCV NS5B polymerase inhibitors through a combination of molecular docking, 3D-QSAR and virtual screening.
abstract: A combination of the following computational methods: (i) molecular docking, (ii) 3-D Quantitative Structure Activity Relationship Comparative Molecular Field Analysis (3D-QSAR CoMFA), (iii) similarity search and (iv) virtual screening using PubChem database was applied to identify new anthranilic acid-based inhibitors of hepatitis C virus (HCV) replication. A number of known inhibitors were initially docked into the "Thumb Pocket 2" allosteric site of the crystal structure of the enzyme HCV RNA-dependent RNA polymerase (NS5B GT1b). Then, the CoMFA fields were generated through a receptor-based alignment of docking poses to build a validated and stable 3D-QSAR CoMFA model. The proposed model can be first utilized to get insight into the molecular features that promote bioactivity, and then within a virtual screening procedure, it can be used to estimate the activity of novel potential bioactive compounds prior to their synthesis and biological tests.
authors.affiliation: a Department of Chemoinformatics , NovaMechanics Ltd. , Nicosia , Cyprus and.|b Department of Chemistry, Laboratory of Organic Chemistry , University of Athens , Athens , Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Vrontaki
authors.affiliation: a Department of Chemoinformatics , NovaMechanics Ltd. , Nicosia , Cyprus and.
authors.forename: Georgia
authors.initials: G
authors.lastname: Melagraki
authors.affiliation: b Department of Chemistry, Laboratory of Organic Chemistry , University of Athens , Athens , Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
authors.affiliation: a Department of Chemoinformatics , NovaMechanics Ltd. , Nicosia , Cyprus and.
authors.forename: Antreas
authors.initials: A
authors.lastname: Afantitis
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000737:chemistry / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: 3D-QSAR CoMFA; HCV replication inhibitors; PubChem database; molecular docking; virtual screening