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.