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.
Highlights
Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation
Comparative reconstruction of S‐glycoprotein in human coronavirus (HCoV) The reconstruction of virus–host interactome was carried out using the Random walk with restart (RWR) algorithm to explore the human protein–protein interactions (PPI) network and the multilayer PPI platform enriched with gene expression data sets. 259 sequences of CoVs, infecting different animal hosts (Additional file 1: Table S1), were downloaded by GSAID and NCBI database in order to evaluate the variability in the S gene
Structure of S‐glycoprotein CoVs To evaluate the diversity along the full genome, pairwise distance was calculated on 259 HCoV genomes
Summary
Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. During the past 2 decades, two highly pathogenic HCoVs, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERSCoV), have led to global epidemics with high morbidity and mortality [6]. In this period, a large amount of experimental data associated with the two infections has allowed to better understand molecular mechanism(s) of coronavirus infection, and enhance pathways for developing new drugs, diagnostics and vaccines and identification of host factors stimulating (proviral factors) or restricting (antiviral factors) infection remains poorly understood [7]. ACE2, expressed in type 2 alveolar cells in the lung, has been identified as receptor of SARS-CoV and SARS-CoV-2, while dipeptidyl peptidase DPP4 was identified as the specific receptor for MERS-CoV [10, 11]
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