Article ; Online: COVID-19: viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection.
Journal of translational medicine
2020 Volume 18, Issue 1, Page(s) 233
Abstract: ... and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was ... in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein ... and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked ...
| Abstract | Background: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. Methods: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. Results: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. Conclusions: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets. |
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| MeSH term(s) | Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/genetics ; Coronavirus Infections/virology ; Gene Regulatory Networks ; Host-Pathogen Interactions ; Humans ; Membrane Glycoproteins/metabolism ; Models, Biological ; Pandemics ; Pneumonia, Viral/genetics ; Pneumonia, Viral/virology ; Protein Interaction Mapping ; SARS-CoV-2 ; Signal Transduction/genetics ; Viral Envelope Proteins |
| Chemical Substances | Membrane Glycoproteins ; Viral Envelope Proteins |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2020-06-10 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 1479-5876 |
| ISSN (online) | 1479-5876 |
| DOI | 10.1186/s12967-020-02405-w |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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