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Looking for pathways related to COVID-19: confirmation of pathogenic mechanisms by SARS-CoV-2-host interactome.
Messina, Francesco; Giombini, Emanuela; Montaldo, Chiara; Sharma, Ashish Arunkumar; Zoccoli, Antonio; Sekaly, Rafick-Pierre; Locatelli, Franco; Zumla, Alimuddin; Maeurer, Markus; Capobianchi, Maria R; Lauria, Francesco Nicola; Ippolito, Giuseppe.
  • Messina F; National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.
  • Giombini E; National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.
  • Montaldo C; National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.
  • Sharma AA; Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
  • Zoccoli A; National Institute of Nuclear Physics (INFN), Bologna, Italy.
  • Sekaly RP; Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
  • Locatelli F; Department of Pediatric Hematology and Oncology IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
  • Zumla A; Department of Infection, Division of Infection and Immunity, University College London, and National Institutes of Health and Research Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.
  • Maeurer M; Champalimaud Centre for the Unknown, Lisbon, Portugal.
  • Capobianchi MR; Medical Clinic, University of Mainz, Mainz, Germany.
  • Lauria FN; National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.
  • Ippolito G; National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.
Cell Death Dis ; 12(8): 788, 2021 08 12.
Article in English | MEDLINE | ID: covidwho-1356553
Preprint
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ABSTRACT
In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level, but the mechanisms of interaction between host and SARS-CoV-2, determining the grade of COVID-19 severity, are still unknown. We provide a network analysis on protein-protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred, applying an explorative algorithm (Random Walk with Restart, RWR) triggered by 28 proteins of SARS-CoV-2. The analysis of PPI allowed to estimate the distribution of SARS-CoV-2 proteins in the host cell. Interactome built around one single viral protein allowed to define a different response, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, the network-based approach highlighted a possible direct action of ORF3a and NS7b to enhancing Bradykinin Storm. This network-based representation of SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Language: English Journal: Cell Death Dis Year: 2021 Document Type: Article Affiliation country: S41419-021-03881-8

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Language: English Journal: Cell Death Dis Year: 2021 Document Type: Article Affiliation country: S41419-021-03881-8