Identification of natural lead molecules as potential cruzipain inhibitors and decoding the interaction mechanism for the treatment of Chagas disease: a computational biology analysis.

Chagas disease has grown into a serious public health threat, with a high morbidity rate, major social impact, and global neglect. Therapeutic adhesion, unwanted side-effects, and resistance make its present therapy ineffective. Discovery of more effective drugs is hence needed. Using natural compounds conjointly with computational methods helps better to find promising compounds, speeding up drug discovery process and reducing its cost. In the present study, a docking protocol against cruzipain (PDB: 3l06), an important druggable target, was applied to a library of 50 sorted natural compounds. Compounds were further analysed for binding mode and interactions with cruzipain active site, conformational alignment studies and pharmacokinetic studies so as to predict their plausible anti-cruzipain mechanism. The results provided computational insights into the molecular interaction of naturals against cruzipain. Study also lead to identification of Hinokiflavone; BA = -10.2 kcal mol as reasonably promising potential natural cruzipain inhibitor.