In-silico analysis of SARS-CoV-2 N protein host interactors involved in Parkinson’s Disease and Dementia

Abstract

Severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) is a highly pathogenic and contagious coronavirus that first surfaced in late 2019. The genome encodes four major structural proteins, non-structural proteins and accessory proteins. The nucleocapsid (N) protein of SARS-CoV-2 is an evolutionarily conserved RNA-binding protein that is abundant and plays a critical role in packaging the viral genome. Researchers have explored its potential as a target for therapeutic purposes. People with pre-existing neurological conditions like Parkinson’s disease (PD) and dementia have been recognised as a high-risk population for severe COVID-19 illness as SARS-CoV-2 has been reported to cause deterioration of the symptoms of these diseases. This study aims to identify the shared human interactors of SARS-CoV-2 N protein, PD and dementia. Proteins involved were retrieved from databases, and protein-protein interaction networks were created and visualized in Cytoscape. Individual intersection networks of SARS-CoV-2 N protein with PD and dementia resulted in 46 and 26 proteins, respectively, while intersection networks of SARS-CoV-2 N protein, PD and dementia resulted in 15 common proteins. Seed proteins were identified from network clusters and their Gene Ontology (GO) analysis revealed their involvement in several biological processes. Valosin-containing-protein (VCP) was found to be the only seed protein involved during the co-occurrence of SARS-CoV-2 N protein infection, PD and dementia and is mainly concerned with the regulation of the ubiquitin-proteasome system (UPS). Further, gene enrichment analysis of the identified 15 common proteins was conducted using the DAVID tool, followed by the identification of 7 druggable targets using the Therapeutic Target Database (TTD) and DrugBank. Studying the biological functions of the identified host-protein interactors is crucial for understanding the progression of the disease at a molecular level. Moreover, approved therapeutic compounds against the potential drug target proteins can also be utilized to develop effective treatments.