Abstract. Dengue, one of the most prevalent mosquito-borne viral infectious diseases of the twenty-first century, affects approximately 100–400 million individuals worldwide. The lack of definitive treatment has led to several in vitro and in silico investigations for potential antivirals. The RNA helicase of the dengue virus (DENV) is a vital protein that is important in viral replication. This study analyzed the antiviral activity of the flavanone naringenin and its derivatives through in silico and in vitro methods, targeting the DENV NS3 helicase enzyme. In this study, in silico screening based on molecular docking and ADMET properties of 20 derivatives of naringenin identified molecules such as 6-fluoro naringenin as the suitable compound. Further, comparative MD simulations and an MM-PBSA study for complexes like NS3-naringenin, NS3-6-fluoronaringenin, and NS3-ST-610 (standard inhibitor molecule) identified that naringenin was able to form a stable complex with the NS3 helicase enzyme of DENV2. These findings of the present study predict the promising anti-dengue nature of the compound naringenin as a replication inhibitor.

 

Key words: dengue virus,NS3 helicase, naringenin, molecular docking, molecular dynamics simulation, antiviral activity