In Silico Prediction of the Phosphorylation of NS3 as an Essential Mechanism for Dengue Virus Replication and the Antiviral Activity of Quercetin
Abstract
Simple Summary Dengue is a mosquito-borne virus that infects up to 400 million people worldwide annually. Dengue infection triggers high fever, severe body aches, rash, low platelet count, and could lead to Dengue hemorrhagic fever (DHF) in some cases. There is currently no cure, nor a broadly effective vaccine. The interaction of two viral proteins, nonstructural Proteins 3 and 5 (NS3 and NS5), is required for viral replication in the infected host’s cells. Our computational modeling of NS3 suggested that phosphorylation of a serine residue at position 137 of NS3 by a specific c-Jun N-terminal kinase (JNK) enhances viral replication by increasing the interaction of NS3 and NS5 through structural changes in amino acid residues 49–95. Experimental studies have shown that inhibition of JNK prevents viral replication and have suggested that the plants’ flavonoid Quercetin, Agathis flavone, and Myricetin inhibit Dengue infection. Our molecular simulations revealed that Quercetin binds NS3 and obstructs serine 137 phosphorylation, which may decrease viral replication. This work offers a molecular mechanism that can be used for anti-Dengue drug development. Abstract Dengue virus infection is a global health problem for which there have been challenges to obtaining a cure. Current vaccines and anti-viral drugs can only be narrowly applied in ongoing clinical trials. We employed computational methods based on structure-function relationships between human host kinases and viral…
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