In Silico Elucidation of Potent Inhibitors from Natural Products for Nonstructural Proteins of Dengue Virus

Abstract

Medicinal plants have been used from the beginning of human civilization against various health complications. Dengue virus (DENV) has emerged as one of the most widespread viruses in tropical and subtropical countries. Yet no clinically approved antiviral drug is available to combat DENV infection. Consequently, the search for novel antidengue agents from medicinal plants has assumed more insistence than in previous days. This study has focused on 31 potential antidengue molecules from secondary metabolites to examine their inhibitory activity against DENV nonstructural proteins through molecular docking and pharmacokinetics studies. In this research, the wet lab experiments were tested on a computational platform. Agathisflavone and pectolinarin are the top-scored inhibitors of DENV NS2B/NS3 protease and NS5 polymerase, respectively. Epigallocatechin gallate, Pinostrobin, Panduratin A, and Pectolinarin could be potential lead compounds against NS2B/NS3 protease, while acacetin-7-O-rutinoside against NS5 polymerase. Moreover, agathisflavone (LD50= 1430 mg/kg) and pectolinarin (LD50= 5000 mg/kg) exhibited less toxicity than nelfinavir (LD50= 600 mg/kg) and balapiravir (LD50 = 824 mg/kg), and the reference drugs. Further research on clinical trials is required to analyze the therapeutic efficacy of these metabolites to develop new potential drug candidates against different serotypes of DENV.