COVID-19: Viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

Francesco Messina, Emanuela Giombini, Chiara Agrati, Francesco Vairo, Tommaso Ascoli Bartoli, Samir Al Moghazi, Mauro Piacentini, Franco Locatelli, Gary Kobinger, Markus Maeurer, Markus Maeurer, Alimuddin Zumla, Alimuddin Zumla, Maria R. Capobianchi, Francesco Nicola Lauria, Giuseppe Ippolito

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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.

Original languageEnglish (US)
Article number233
JournalJournal of Translational Medicine
Volume18
Issue number1
DOIs
StatePublished - Jun 10 2020
Externally publishedYes

Keywords

  • Coronavirus infection
  • Spike glycoprotein
  • Virus-host interactome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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