Potential Antiviral Drug Against Human Papillomavirus Type 16 Through Indandione-Containing Inhibitors of E1-E2 Protein Interaction

Abstract

Cervical cancer, predominantly caused by HPV infection, is ranked among the most emerging cause of cancer across the world, and is the second most common cause of female cancer in India. The high-risk HPV16 and HPV18 strains of the virus are the most prevalent causative agents of this disease. Among the various proteins produced by the virus, E1 and E2 are the major proteins involved in viral replication and thus are suitable targets for antiviral therapy. Studies have shown that the E1-E2-ori complex formed during DNA replication can be effectively interrupted by a specific class of Indandione-containing inhibitor compounds in HPV11. This study focuses on observing the efficacy of such ligands on the E1-E2-ori complex in HPV16, as well as the modifications required to improve the efficacy of the drugs. The targets were selected after a thorough literature study and their protein sequences were retrieved from NCBI to model a 3D structure using homology modeling method on the SWISS-MODEL platform. The ligand molecule and its derivatives were obtained from various literature and databases. Molecular docking was performed using PyRx, Chimera 2.0 software, and Discovery Studio software. The ligand molecules were tested for ADMET using pkCSM platform and SwissADME platform. This study aims to direct research towards the development of HPV treatments, which is necessary to overcome the limitations of vaccines and bridge the socio-economic divide made by the uneven distribution of HPV vaccines and the social stigma associated with the disease.