Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis

Abstract

COVID-19 (Coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the pathophysiology of this deadly virus is complex and largely unknown, we employ a network biology-fueled approach and integrated multiomics data pertaining to lung epithelial cells-specific coexpression network and human interactome to generate Calu-3-specific human-SARS-CoV-2 Interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 target central nodes of host-viral network that participate in core functional pathways. Network centrality analyses discover 28 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm. Overall, our network centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into SARS-CoV-2 pathogenicity.

Brain Disease Network Analysis to Elucidate the Neurological Manifestations of COVID-19

“…Intriguingly, all the 16 hub genes are targets of more than one SARS-CoV-2 protein (Table 1 ), out of which NPM1, SNW1, GRB2, HSP90AA1, and ELAVL1 are the target of several SARS-CoV-2 proteins. These findings are consistent with previous findings which indicates that an individual viral protein can target multiple host proteins and several viral proteins can interact with the same host protein [ 25 , 26 , 55 – 57 ].…”

Update on therapeutic approaches and emerging therapies for SARS-CoV-2 virus

“…Moreover, integration of drug-target networks of the top 16 drug candidates produced of potent drug combinations using a complementary exposure technique (Chen et al, 2020b). Other studies have also shown the potential of using a network based methodology to screen possible drug targets for SARS-CoV-2 (Hofmarcher et al, 2020;Kumar et al, 2020;Li et al, 2020c).The method is a quick way of identifying drug targets. However, it is not designed to produce drugs, but is a useful tool for prediction of new drugs, and combinations, and reduces the period of drug screening and development.…”

Computational Analysis of the Global Effects of Ly6E in the Immune Response to Coronavirus Infection Using Gene Networks

“…As it is the case of Giotis et al [ 52 ], these studies often involve global transcriptome analyses, via RNA-seq or microarrays, together with computational efforts, which intend to screen the key elements of the immune system that are required for the appropriate response. This approach ultimately leads experimental research through predictive analyses, as in the case of co-expression gene networks [ 53 ].…”