In silico study on assembly of Dengue virus capsid protein with core histone proteins

Abstract

The Dengue virus (DENV), a member of the Flaviviridae family, is a rapidly spreading pathogen that infects millions of people every year causing severe illness. The capsid (C) protein is in charge of assembling the viral RNA into a nucleocapsid. A significant amount of capsid protein relocates to the nucleus, although viral replication takes place in the cytoplasm. DENV C interacts with the four core histones according to earlier research. Therefore, DENV C functions to bind DNA and interfere with the assembly of nucleosomes through heterodimerization with core histones. Using coarse-grained in silico assembly simulations and comprehensive MD simulations to examine the interaction between the proteins, we have elucidated on the pattern of interaction between the DENV C protein and the histone proteins. Here it was seen that the interaction strength of DENV C and histones is as follows: H3> H2B> H2A> H4 with all interactions being highly stable. Our study also identifies critical residues (majorly hydrophobic residues in the hydrophobic pocket and H4 helix) in the DENV C protein responsible for these interactions. This study opens up new possibilities for antiviral drug design by advancing our understanding of the molecular interactions between viral proteins and host cell machinery.