Prediction of protein-protein interactions in dengue virus coat proteins guided by low resolution cryoEM structures

In the present analysis, starting from Cα positions of low resolution cryo electron microscopic structures the residue level details of protein-protein interaction interfaces of dengue virus coat proteins have been predicted. By comparing the preexisting structures of virus in different phases of life cycle, the changes taking place in these predicted protein-protein interaction interfaces were followed as a function of maturation process of the virus. Besides changing the current notion about the presence of only homodimers in the mature viral coat, the present analysis indicated presence of a proline-rich motif at the protein-protein interaction interface of the coat protein. Investigating the conservation status of these seemingly functionally crucial residues across other members of flaviviridae family enabled dissecting common mechanisms used for infections by these viruses.Thus, using computational approach the present analysis has provided better insights into the preexisting low resolution structures of virus assemblies, the findings of which can be made use of in designing effective antivirals against these deadly human pathogens.Dengue viruses (DENV), belonging to the flaviviridae family, are the causative agents of dengue fever and dengue hemorrhagic fever. The four serotypes DENV1, DENV2, DENV3 & DENV4 rely upon Aedes aegypti mosquitoes for their transmission between the vertebrate hosts [1]. In the recent past, there had been a resurgence of these viruses as deadly human pathogens with about 50 million infections occurring annually [1]. Yet, no vaccines or specific effective antivirals are currently available. The conventional approach towards vaccine development has not been greatly successful in these viruses[1]. Due to the presence of four different serotypes of the virus, prevention of antibody dependent enhancement (ADE) of the infection has turned out to be rather challenging [2]. Hence, new avenues of vaccine development are being explored [3]. T