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

Autor: Alimuddin Zumla, Tommaso Ascoli Bartoli, Francesco Messina, Gary P. Kobinger, Chiara Agrati, Markus Maeurer, Mauro Piacentini, Francesco Vairo, Giuseppe Ippolito, Franco Locatelli, Emanuela Giombini, Francesco Nicola Lauria, Samir Al Moghazi, Maria Rosaria Capobianchi
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Chemokine
viruses
Pneumonia
Viral
Gene regulatory network
lcsh:Medicine
Computational biology
Virus-host interactome
medicine.disease_cause
Models
Biological
Interactome
General Biochemistry
Genetics and Molecular Biology
Transcriptome
Pathogenesis
03 medical and health sciences
Betacoronavirus
0302 clinical medicine
Viral Envelope Proteins
Protein Interaction Mapping
medicine
Coronavirus infection
Humans
Gene Regulatory Networks
Pandemics
Gene
Coronavirus
Virus–host interactome
Membrane Glycoproteins
Innate immune system
biology
SARS-CoV-2
Research
lcsh:R
COVID-19
virus diseases
General Medicine
biochemical phenomena
metabolism
and nutrition
Spike glycoprotein
Phenotype
respiratory tract diseases
coronavirus infection
spike glycoprotein
virus-host interactome
030104 developmental biology
Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA
030220 oncology & carcinogenesis
Host-Pathogen Interactions
biology.protein
Coronavirus Infections
Signal Transduction
Zdroj: Journal of Translational Medicine
Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-10 (2020)
Journal of translational medicine, 18(1):233
ISSN: 1479-5876
Popis: 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.
Databáze: OpenAIRE
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