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bioRxiv · 10.1101/2020.05.07.082487

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

Messina, F.·Giombini, E.·Agrati, C.·Vairo, F.·Ascoli Bartoli, T.·Al Moghazi, S.·Piancentini, M.·Locatelli, F.·Kobinger, G.·Maeurer, M.·Zumla, A.·Capobianchi, M. R.·Lauria, F. N.·Ippolito, G.
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Abstract

BackgroundEpidemiological, 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. MethodsWe 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. ResultsAlthough 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. ConclusionsIn 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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Messina, F., Giombini, E., Agrati, C., Vairo, F., Ascoli Bartoli, T., Al Moghazi, S., Piancentini, M., Locatelli, F., Kobinger, G., Maeurer, M., Zumla, A., Capobianchi, M. R., Lauria, F. N., Ippolito, G.. 2020-05-07. COVID-19: Viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection.. https://doi.org/10.1101/2020.05.07.082487

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