Computational analysis of human host binding partners of chikungunya and dengue viruses during coinfection.

ABSTRACT

Mosquito-borne viral diseases like chikungunya and dengue infections can cause severe illness and have become major public health concerns. Chikungunya virus (CHIKV) and dengue virus (DENV) infections share similar primary clinical manifestations and are transmitted by the same vector. Thus, the probability of their coinfection gets increased with more severe clinical complications in the patients. The present study was undertaken to elucidate the common human interacting partners of CHIKV and DENV proteins during coinfection. The viral-host protein-protein interactome was constructed using Cytoscape. Subsequently, significant host interactors were identified during coinfection. The network analysis elucidated 57 human proteins interacting with both CHIKV and DENV, represented as hub-bottlenecks. The functional and biological analyses of the 40 hub-bottlenecks revealed that they are associated with phosphoinositide 3-kinases (PI3K)/AKT, p53 signaling pathways, regulation of cell cycle and apoptosis during coinfection. Moreover, the molecular docking analysis uncovered the tight and robust binding of selected hub-bottlenecks with CHIKV/DENV proteins. Additionally, 23 hub-bottlenecks were predicted as druggable candidates that could be targeted to eradicate the host-viral interactions. The elucidated common host binding partners during DENV and CHIKV coinfection as well as indicated approved drugs can support the therapeutics development.