tetano
Editor, Senior Moderator
J Transl Med
. 2020 Jun 10;18(1):233.
doi: 10.1186/s12967-020-02405-w.
COVID-19: Viral-Host Interactome Analyzed by Network Based-Approach Model to Study Pathogenesis of SARS-CoV-2 Infection
Francesco Messina[SUP] 1 [/SUP], Emanuela Giombini[SUP] 1 [/SUP], Chiara Agrati[SUP] 1 [/SUP], Francesco Vairo[SUP] 1 [/SUP], Tommaso Ascoli Bartoli[SUP] 1 [/SUP], Samir Al Moghazi[SUP] 1 [/SUP], Mauro Piacentini[SUP] 1 2 [/SUP], Franco Locatelli[SUP] 3 [/SUP], Gary Kobinger[SUP] 4 [/SUP], Markus Maeurer[SUP] 5 6 [/SUP], Alimuddin Zumla[SUP] 7 8 [/SUP], Maria R Capobianchi[SUP] 9 [/SUP], Francesco Nicola Lauria[SUP] 1 [/SUP], Giuseppe Ippolito[SUP] 1 [/SUP], COVID 19 INMI Network Medicine for IDs Study Group
Collaborators, Affiliations
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.
Keywords: Coronavirus infection; Spike glycoprotein; Virus–host interactome.
. 2020 Jun 10;18(1):233.
doi: 10.1186/s12967-020-02405-w.
COVID-19: Viral-Host Interactome Analyzed by Network Based-Approach Model to Study Pathogenesis of SARS-CoV-2 Infection
Francesco Messina[SUP] 1 [/SUP], Emanuela Giombini[SUP] 1 [/SUP], Chiara Agrati[SUP] 1 [/SUP], Francesco Vairo[SUP] 1 [/SUP], Tommaso Ascoli Bartoli[SUP] 1 [/SUP], Samir Al Moghazi[SUP] 1 [/SUP], Mauro Piacentini[SUP] 1 2 [/SUP], Franco Locatelli[SUP] 3 [/SUP], Gary Kobinger[SUP] 4 [/SUP], Markus Maeurer[SUP] 5 6 [/SUP], Alimuddin Zumla[SUP] 7 8 [/SUP], Maria R Capobianchi[SUP] 9 [/SUP], Francesco Nicola Lauria[SUP] 1 [/SUP], Giuseppe Ippolito[SUP] 1 [/SUP], COVID 19 INMI Network Medicine for IDs Study Group
Collaborators, Affiliations
- PMID: 32522207
- DOI: 10.1186/s12967-020-02405-w
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.
Keywords: Coronavirus infection; Spike glycoprotein; Virus–host interactome.