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

Autor: Jean-Michel Claverie
Přispěvatelé: Information génomique et structurale (IGS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), IGS laboratory (UMR CNRS-AMU 7256)
Rok vydání: 2020
Předmět:
MESH: Inflammation
0301 basic medicine
MESH: Coronavirus Infections
viruses
lcsh:QR1-502
interferon-stimulated gene
Coronavirus Papain-Like Proteases
Sequence Homology
ACE2
MESH: Amino Acid Sequence
Viral Nonstructural Proteins
medicine.disease_cause
lcsh:Microbiology
0302 clinical medicine
MESH: Sequence Homology
STAT1
Coronavirus
biology
virus diseases
3. Good health
STAT1 Transcription Factor
Infectious Diseases
Severe acute respiratory syndrome-related coronavirus
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Middle East Respiratory Syndrome Coronavirus
MESH: Betacoronavirus
Angiotensin-Converting Enzyme 2
medicine.symptom
Coronavirus Infections
Cytokine Release Syndrome
Opinion
MESH: ADP-Ribosylation
MESH: Pandemics
Pneumonia
Viral
MESH: SARS Virus
Virulence
Context (language use)
Inflammation
Peptidyl-Dipeptidase A
PARP14
Virus
Betacoronavirus
03 medical and health sciences
ADP-Ribosylation
Virology
medicine
Humans
Amino Acid Sequence
Pandemics
de-MARylation
MESH: Humans
SARS-CoV-2
Interferon-stimulated gene
MESH: Middle East Respiratory Syndrome Coronavirus
COVID-19
medicine.disease
MESH: Peptidyl-Dipeptidase A
030104 developmental biology
MESH: Pneumonia
Viral
inflammation
MESH: Cytokine Release Syndrome
biology.protein
MESH: Viral Nonstructural Proteins
MESH: STAT1 Transcription Factor
Cytokine storm
030217 neurology & neurosurgery
Zdroj: Viruses
Viruses, 2020, 12 (6), pp.646. ⟨10.3390/v12060646⟩
Viruses, MDPI, 2020, 12 (6), pp.646. ⟨10.3390/v12060646⟩
Viruses, Vol 12, Iss 646, p 646 (2020)
ISSN: 1999-4915
DOI: 10.3390/v12060646
Popis: International audience; 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.
Databáze: OpenAIRE
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