Computational approach to decipher cellular interactors and drug targets during co-infection of SARS-CoV-2, Dengue, and Chikungunya virus

Abstract

The world is reeling under severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and it will be frightening if compounded by other co-existing infections. The co-occurrence of the Dengue virus (DENV) and Chikungunya virus (CHIKV) has been into existence, but recently the co-infection of DENV and SARS-CoV-2 has been reported. Thus, the possibility of DENV, CHIKV, and SARS-CoV-2 co-infection could be predicted in the future with enhanced vulnerability. It is essential to elucidate the host interactors and the connected pathways to understand the biological insights. The in silico approach using Cytoscape was exploited to elucidate the common human proteins interacting with DENV, CHIKV, and SARS-CoV-2 during their probable co-infection. In total, 17 interacting host proteins were identified showing association with envelope, structural, non-structural, and accessory proteins. Investigating the functional and biological behaviour using PANTHER, UniProtKB, and KEGG databases uncovered their association with several cellular pathways including, signaling pathways, RNA processing and transport, cell cycle, ubiquitination, and protein trafficking. Withal, exploring the DrugBank and Therapeutic Target Database, total seven druggable host proteins were predicted. Among all integrin beta-1, histone deacetylase-2 (HDAC2) and microtubule affinity-regulating kinase-3 were targeted by FDA approved molecules/ drugs. Furthermore, HDAC2 was predicted to be the most significant target, and some approved drugs are available against it. The predicted druggable targets and approved drugs could be investigated to obliterate the identified interactions that could assist in inhibiting viral infection.

Keywords: Cellular interactors; Covid-19; Viral inhibitor; Viral-host protein interactions.