Network for network concept offers new insights into host- SARS-CoV-2 protein interactions and potential novel targets for developing antiviral drugs

• Published in: Computers in biology and medicine 2022-07, Vol.146, p.105575-105575, Article 105575
• Main Authors: Eskandarzade, Neda, Ghorbani, Abozar, Samarfard, Samira, Diaz, Jose, Guzzi, Pietro H., Fariborzi, Niloofar, Tahmasebi, Ahmad, Izadpanah, Keramatollah
• Format: Article
• Language: English
• Subjects: Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Antiviral drugs; Binding sites; Coronaviruses; COVID-19; COVID-19 Drug Treatment; Disintegration; Drugs; Enzymes; Gene network; Genes; Genomes; Graph theory; Humans; Infectivity; Influenza; Ligands; Metabolism; Middle East respiratory syndrome; Ontology; Organs; Pandemics; Pathogenicity; Pathogens; Pharmaceutical industry; Protein interaction; Protein-protein interactions; Proteins; Proteins - metabolism; Proteomics; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Tropism; Viral diseases; Virulence; Virus-host interactome; Viruses; Visualization
• ISSN: 0010-4825; 1879-0534
• DOI: 10.1016/j.compbiomed.2022.105575

SARS-CoV-2, the causal agent of COVID-19, is primarily a pulmonary virus that can directly or indirectly infect several organs. Despite many studies carried out during the current COVID-19 pandemic, some pathological features of SARS-CoV-2 have remained unclear. It has been recently attempted to address the current knowledge gaps on the viral pathogenicity and pathological mechanisms via cellular-level tropism of SARS-CoV-2 using human proteomics, visualization of virus-host protein-protein interactions (PPIs), and enrichment analysis of experimental results. The synergistic use of models and methods that rely on graph theory has enabled the visualization and analysis of the molecular context of virus/host PPIs. We review current knowledge on the SARS-COV-2/host interactome cascade involved in the viral pathogenicity through the graph theory concept and highlight the hub proteins in the intra-viral network that create a subnet with a small number of host central proteins, leading to cell disintegration and infectivity. Then we discuss the putative principle of the “gene-for-gene and “network for network” concepts as platforms for future directions toward designing efficient anti-viral therapies. •Gene for Gene theory should be replaced with Network for Network PPI for interaction between virus and host.•PPIs studies lead to further knowledge on the characterization of disease progression.•Host PPI networks can determine the key host proteins associated with disease pathways.•Drug design approaches must focus on targeting proteins that have synergistic effects on the viral-host PPI network.