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

Posted on 19.06.2020 - 03:40
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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Messina, Francesco; Giombini, Emanuela; Agrati, Chiara; Vairo, Francesco; Ascoli Bartoli, Tommaso; Al Moghazi, Samir; et al. (2020): COVID-19: viral–host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5016785.v2
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Journal of Translational Medicine

AUTHORS (14)

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
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