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COVID-19: viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection.
J Transl Med. 2020 06 10; 18(1):233.JT

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.

Authors+Show Affiliations

National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy. Department of Biology, University of Rome "Tor Vergata", Rome, Italy.Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy.Département de Microbiologie-Infectiologie et d'Immunologie, Université Laval, Quebec, QC, Canada.ImmunoSurgery Unit, Champalimaud Centre for the Unknown, Lisbon, Portugal. I. Medizinische Klinik Johannes Gutenberg-Universität, University of Mainz, Mainz, Germany.Department of Infection, Division of Infection and Immunity, University College London, London, UK. National Institute for Health Research Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy. maria.capobianchi@inmi.it.National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32522207

Citation

Messina, Francesco, et al. "COVID-19: Viral-host Interactome Analyzed By Network Based-approach Model to Study Pathogenesis of SARS-CoV-2 Infection." Journal of Translational Medicine, vol. 18, no. 1, 2020, p. 233.
Messina F, Giombini E, Agrati C, et al. COVID-19: viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection. J Transl Med. 2020;18(1):233.
Messina, F., Giombini, E., Agrati, C., Vairo, F., Ascoli Bartoli, T., Al Moghazi, S., Piacentini, M., Locatelli, F., Kobinger, G., Maeurer, M., Zumla, A., Capobianchi, M. R., Lauria, F. N., & Ippolito, G. (2020). COVID-19: viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection. Journal of Translational Medicine, 18(1), 233. https://doi.org/10.1186/s12967-020-02405-w
Messina F, et al. COVID-19: Viral-host Interactome Analyzed By Network Based-approach Model to Study Pathogenesis of SARS-CoV-2 Infection. J Transl Med. 2020 06 10;18(1):233. PubMed PMID: 32522207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - COVID-19: viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection. AU - Messina,Francesco, AU - Giombini,Emanuela, AU - Agrati,Chiara, AU - Vairo,Francesco, AU - Ascoli Bartoli,Tommaso, AU - Al Moghazi,Samir, AU - Piacentini,Mauro, AU - Locatelli,Franco, AU - Kobinger,Gary, AU - Maeurer,Markus, AU - Zumla,Alimuddin, AU - Capobianchi,Maria R, AU - Lauria,Francesco Nicola, AU - Ippolito,Giuseppe, AU - ,, Y1 - 2020/06/10/ PY - 2020/04/25/received PY - 2020/06/04/accepted PY - 2020/6/12/entrez PY - 2020/6/12/pubmed PY - 2020/6/24/medline KW - Coronavirus infection KW - Spike glycoprotein KW - Virus–host interactome SP - 233 EP - 233 JF - Journal of translational medicine JO - J Transl Med VL - 18 IS - 1 N2 - 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. SN - 1479-5876 UR - https://www.unboundmedicine.com/medline/citation/32522207/COVID_19:_viral_host_interactome_analyzed_by_network_based_approach_model_to_study_pathogenesis_of_SARS_CoV_2_infection_ L2 - https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02405-w DB - PRIME DP - Unbound Medicine ER -