Pharmacophore Modeling and Molecular Docking Studies of potential inhibitors to E6 PBM–PDZ from Human Papilloma Virus (HPV)

High-risk human papillomaviruses (HPVs) are known to cause cervical cancer. Vaccines are now available to prevent HPV infection. However, a clinically approved drug is yet not available to treat HPV. The PDZ(PSD-95/Dlg/ZO-1)-binding motif (PBM) in the E6 protein of HPVs targets the PDZ domain (known to be associated with oncogenesis) for degradation. Therefore, it is of interest to study PBM-PDZ interaction towards its possible inhibition with a potential inhibitor. Thus, four pharmocophore models of PBM-PDZ complex were developed. In order to obtain potent small molecules for its inhibition, a commercial compound database was screened using both these pharmacophore models and molecule docking method. These efforts identified four potential compounds (1-4) towards its inhibition with the docking scores range -18.2 to -15.0.