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 coarsegrained 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.