AN IN SILICO STUDY ON HIV-1 PROTEASE WILD-TYPE AND MUTANT WITH INHIBITORS FROM ANNONA SQUAMOSA

Human immunodeficiency virus (HIV) is a lent virus that cause acquired immunodeficiency syndrome (AIDS), a state in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. HIV-1 protease is a retroviral aspartyl protease (retropepsin) that is essential for the life-cycle of HIV, the retrovirus that causes AIDS. HIV Wild type (PDB: 3EKV) and Mutated (PDB: 3NU9) proteins structures were retrieved from Protein Data Bank in order to check the consistency of ligand’s interactions even if mutated viral attack is present. Docking is frequently used to predict the binding orientation of small moleculedrug candidates to their protein targets in order to in turn predict the affinity and activity of the small molecule. Docking study of the target protein was done with natural compounds derived from Annona Squamosa to find the preferred orientation and binding affinity of drug with target protein using scoring functions. Annona squamosa is a small, well-branched tree or shrub from the family Annonaceae that bears edible fruits called sugar-apples. Chemical constituents found in extracts of the seeds, bark, and leaves of this tree. Phytochemicals screened for Glide HTVS followed by SP (Standard Precision) docking showed good interaction with the target. The anti HIV compounds that yielded a fitness score of more than -5 were further subjected to Molecular dynamics simulation (MDS). Higenamine and Romerolidine shows good binding affinity with the target proteins 3EKV and 3NU9 respectively and that can be a potential target for Aids.