Evaluation of Biphenylalanine and Its Derivatives as Potential HIV-1 gp120 Attachment Inhibitors Based on Molecular Docking, CD4 Capture ELISA and Cytotoxicity Analysis

Biphenylalanine and its derivatives (BPAs) are novel attachment inhibitors that target HIV-1 gp120 and prevent its binding to CD4 on host cell, designed via molecular modelling and docking using gp120-CD4 protein complex crystal structure. In this study, molecular docking showed that L-biphenylalanine has highest binding probability than D-biphenylalanine and L-methyl-biphenylalanine and exhibited low negative docked energy. The CD4 capture ELISA experiments indicated that L-biphenylalanine has an IC50 at submicromolar concentration. The Vero cell cytotoxicity test revealed that BPAs were non-toxic up to 400 mu M. L-biphenylalanine fulfils "the Lipinski rule of five" criteria as a good drug candidate.