Searching for anthranilic acid-based thumb pocket 2 HCV NS5B polymerase inhibitors through a combination of molecular docking, 3D-QSAR and virtual screening |
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Authors: | Eleni Vrontaki Thomas Mavromoustakos |
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Institution: | 1. Department of Chemoinformatics, NovaMechanics Ltd., Nicosia, Cyprus and;2. Department of Chemistry, Laboratory of Organic Chemistry, University of Athens, Athens, Greece;3. Department of Chemistry, Laboratory of Organic Chemistry, University of Athens, Athens, Greece |
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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. |
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Keywords: | 3D-QSAR CoMFA HCV replication inhibitors molecular docking PubChem database virtual screening |
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