Off-Target-Based Design of Selective HIV-1 PROTEASE Inhibitors
Copyright policy )Off-Target-Based Design of Selective HIV-1 PROTEASE Inhibitors
The approval of the first HIV-1 protease inhibitors (HIV-1 PRIs) marked a fundamental step in the control of AIDS, and this class of agents still represents the mainstay therapy for this illness. Despite the undisputed benefits, the necessary lifelong treatment led to numerous severe side-effects (metabolic syndrome, hepatotoxicity, diabetes, etc.). The HIV-1 PRIs are capable of interacting with “secondary” targets (off-targets) characterized by different biological activities from that of HIV-1 protease. In this scenario, the in-silico techniques undoubtedly contributed to the design of new small molecules with well-fitting selectivity against the main target, analyzing possible undesirable interactions that are already in the early stages of the research process. The present work is focused on a new mixed-hierarchical, ligand-structure-based protocol, which is centered on an on/off-target approach, to identify the new selective inhibitors of HIV-1 PR. The use of the well-established, ligand-based tools available in the DRUDIT web platform, in combination with a conventional, structure-based molecular docking process, permitted to fast screen a large database of active molecules and to select a set of structure with optimal on/off-target profiles. Therefore, the method exposed herein, could represent a reliable help in the research of new selective targeted small molecules, permitting to design new agents without undesirable interactions.
- University of Palermo Italy
Virtual screening, on/off-targets, Protein Conformation, NCI database, HIV Infections, Ligands, Article, Molecular descriptors, molecular descriptors, Structure-Activity Relationship, HIV Protease, Catalytic Domain, HIV-1 protease, Drug Discovery, Humans, Computer Simulation, DRUDIT, On/off-targets, Molecular Structure, molecular docking, HIV Protease Inhibitors, virtual screening, Ligand-structure based, Molecular Docking Simulation, Drug Design, Molecular docking, ligand-structure based, HIV-1
Virtual screening, on/off-targets, Protein Conformation, NCI database, HIV Infections, Ligands, Article, Molecular descriptors, molecular descriptors, Structure-Activity Relationship, HIV Protease, Catalytic Domain, HIV-1 protease, Drug Discovery, Humans, Computer Simulation, DRUDIT, On/off-targets, Molecular Structure, molecular docking, HIV Protease Inhibitors, virtual screening, Ligand-structure based, Molecular Docking Simulation, Drug Design, Molecular docking, ligand-structure based, HIV-1
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