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A Putative Role of de-Mono-ADP-Ribosylation of STAT1 by the SARS-CoV-2 Nsp3 Protein in the Cytokine Storm Syndrome of COVID-19.
Claverie, Jean-Michel.
  • Claverie JM; Structural & Genomic Information Laboratory (IGS, UMR 7256), Mediterranean Institute of Microbiology (FR3479), Aix-Marseille University and CNRS, 13288 Marseille, France.
Viruses ; 12(6)2020 06 15.
Article in English | MEDLINE | ID: covidwho-598456
ABSTRACT
As more cases of COVID-19 are studied and treated worldwide, it had become apparent that the lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the SARS-CoV-2 virus. I explored the putative causes of this specific feature through a detailed genomic comparison with the closest SARS-CoV-2 relatives isolated from bats, as well as previous coronavirus strains responsible for the previous epidemics (SARS-CoV and MERS-CoV). The high variability region of the nsp3 protein was confirmed to exhibit the most variations between closest strains. It was then studied in the context of physiological and molecular data available in the literature. A number of convergent findings suggest de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a putative cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and help in designing assays to predict the virulence of naturally circulating SARS-like animal coronaviruses.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Nonstructural Proteins / STAT1 Transcription Factor / Betacoronavirus / ADP-Ribosylation / Cytokine Release Syndrome Type of study: Observational study / Prognostic study Limits: Humans Language: English Year: 2020 Document Type: Article Affiliation country: V12060646

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Nonstructural Proteins / STAT1 Transcription Factor / Betacoronavirus / ADP-Ribosylation / Cytokine Release Syndrome Type of study: Observational study / Prognostic study Limits: Humans Language: English Year: 2020 Document Type: Article Affiliation country: V12060646