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

View ORCID ProfileFrancesco Messina, Emanuela Giombini, Chiara Agrati, Francesco Vairo, Tommaso Ascoli Bartoli, Samir Al Moghazi, Mauro Piacentini, Franco Locatelli, Gary Kobinger, Markus Maeurer, Alimuddin Zumla, Maria R. Capobianchi, Francesco Nicola Lauria, Giuseppe Ippolito, COVID 19 INMI Network Medicine for IDs Study Group
doi: https://doi.org/10.1101/2020.05.07.082487
Francesco Messina
1National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy
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  • ORCID record for Francesco Messina
Emanuela Giombini
1National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy
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Chiara Agrati
1National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy
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Francesco Vairo
1National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy
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Tommaso Ascoli Bartoli
1National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy
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Samir Al Moghazi
1National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy
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Mauro Piacentini
1National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy
2Department of Biology, University of Rome “Tor Vergata,” Rome, Italy
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Franco Locatelli
3Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Piazza Sant’Onofrio, 4, 00165 Rome, Italy
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Gary Kobinger
4Département de Microbiologie-Infectiologie et d’Immunologie, Université Laval, Québec City, Québec, Canada
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Markus Maeurer
5Champalimaud Centre for the Unknown, Lisbon, Portugal; I. Medizinische Klinik Johannes Gutenberg-Universität, University of Mainz, 55131 Mainz, Germany
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Alimuddin Zumla
6Department of Infection, Division of Infection and Immunity, University College London, and National Institutes of Health and Research Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK
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Maria R. Capobianchi
1National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy
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  • For correspondence: maria.capobianchi@inmi.it
Francesco Nicola Lauria
1National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy
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Giuseppe Ippolito
1National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy
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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.

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations

    CoVs
    Coronaviruses
    HCoV
    Human Coronavirus
    PPI
    Protein-Protein Interactions
    COEX
    Gene Coexpression data
    SARS-CoV
    Severe Acute Respiratory Syndrome Coronavirus
    MERS-CoV
    Middle East Respiratory Syndrome Coronavirus
    S-glycoprotein
    Spike glycoprotein
    RWR
    Random walk with restart
    FDR
    False Discovery Rate
  • Copyright 
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    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, Alimuddin Zumla, Maria R. Capobianchi, Francesco Nicola Lauria, Giuseppe Ippolito, COVID 19 INMI Network Medicine for IDs Study Group
    bioRxiv 2020.05.07.082487; doi: https://doi.org/10.1101/2020.05.07.082487
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    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, Alimuddin Zumla, Maria R. Capobianchi, Francesco Nicola Lauria, Giuseppe Ippolito, COVID 19 INMI Network Medicine for IDs Study Group
    bioRxiv 2020.05.07.082487; doi: https://doi.org/10.1101/2020.05.07.082487

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