Paritaprevir as a Pan-antiviral Against Different Flaviviruses

Nihar R. Jena ^* Ramprakash Yadav

• PDPM Indian Institute of Information Technology, Design and Manufacturing, Jabalpur, India

To understand the structures, dynamics, and stabilities of some Human Immune Deficiency Virus (HIV) and Hepatitis C virus (HCV) drugs in binding to the Zika virus (ZIKV) NS2B-NS3 protease, 20 known antiviral drugs used against the HIV and HCV proteases were docked into the active site of the NS2B-NS3 protease of the ZIKV. Based on docking scores, 5 drugs, such as Ritonavir, Saquinavir, Indinavir, Paritaprevir, and Lopinavir were shortlisted for the Molecular Dynamics (MD) simulations and free-energy calculations. Among these drugs, the binding of Ritonavir and Paritaprevir with the NS2B-NS3 protease of the ZIKV produced the most stable complexes with the Gibbs binding free energies (Gbind) of -17.443.18 kcal/mol and -14.253.11 kcal/mol respectively. Remarkably, Ritonavir binds to the ZIKV Protease about 12 kcal/mol more strongly compared to its binding to the HIV protease. As the NS2B-NS3 proteases of Dengue virus (DENV) and West Nile virus (WNV) are structurally and functionally similar to that of the ZIKV, the binding of Ritonavir and Paritaprevir to the proteases of DENV and WNV were further studied to identify pan-antivirals. It is found that Paritaprevir can bind to all of these proteases strongly with Gbind lying between -12.762.91 kcal/mol to -17.32.55 kcal/mol. Hence it is proposed that Paritaprevir may further be tested as a potent pan-antiviral against the Zika, West Nile, and Dengue viral diseases.