Molecular modeling studies and comparative analysis on structurally similar HTLV and HIV protease using HIV-PR inhibitors.
Retroviruses are most perilous viral family, which cause much damage to the Homo sapiens. HTLV-1 mechanism found to more similar with HIV-1 and both retroviruses are causative agents of severe and fatal diseases including adult T-cell leukemia (ATL) and the acquired immune deficiency syndrome (AIDS). Both viruses code for a protease (PR) that is essential for replication and therefore represents a key target for drugs interfering with viral infection. In this work, the comparative study of HIV-1 and HTLV-1 PR enzymes through sequence and structural analysis is reported along with approved drugs of HIV-PR. Conformation of each HIV PR drugs have been examined with different parameters of interactions and energy scorings parameters. MD simulations with respect to timescale event of 20 ns favors that, few HIV-PR inhibitors can be more active inside the HTLV-1 PR binding pocket. Overall results suggest that, some of HIV inhibitors like Tipranavir, Indinavir, Darunavir and Amprenavir are having good energy levels with HTLV-1. Due to absence of interactions with MET37, here we report that derivatives of these compounds can be much better inhibitors for targeting HTLV-1 proteolytic activity.
Computer-Aided Drug Design and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University , Karaikudi, Tamil Nadu , India and.
Chandrabose
C
Selvaraj
Poonam
P
Singh
Sanjeev Kumar
SK
Singh
D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004789:Enzyme Activation; D016333:HIV Protease / Q000737:chemistry* / Q000648:ultrastructure*; D017320:HIV Protease Inhibitors / Q000737:chemistry*; D008956:Models, Chemical; D062105:Molecular Docking Simulation / Q000379:methods*; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping
D017320:HIV Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C079711:HTLV-1 protease
Binding energy; HIV-1; HTLV-1; QPLD; interaction energy; protease