Journal Article

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

2020

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: ACE2 / ADP-Ribosylation / ADP-Ribosylation - physiology / Amino Acid Sequence / Amino Acid Sequence - genetics / Angiotensin-Converting Enzyme 2 / animals / Betacoronavirus / Betacoronavirus - genetics / Binding sites / Chiroptera / Coronaviridae / Coronavirus Infections / Coronavirus Infections - pathology / Coronavirus Papain-Like Proteases / Coronaviruses / COVID-19 / COVID-19 infection / Cytokine Release Syndrome / Cytokine Release Syndrome - pathology / Cytokine storm / Cytokines / de-MARylation / disease outbreaks / Disease transmission / Enzymes / Epidemics / Genes / genomics / Humans / Hypotheses / Inflammation / Inflammation - pathology / Inflammation - virology / interferon-stimulated gene / Kinases / Life Sciences / Microbiology and Parasitology / Middle East Respiratory Syndrome Coronavirus / Middle East Respiratory Syndrome Coronavirus - genetics / NSP3 protein / Opinion / Pandemics / PARP14 / Peptidyl-Dipeptidase A / Peptidyl-Dipeptidase A - biosynthesis / Peptidyl-Dipeptidase A - genetics / Phosphorylation / pneumonia / Pneumonia, Viral / Pneumonia, Viral - pathology / Proteins / Respiratory diseases / Ribosylation / SARS Virus / SARS Virus - genetics / SARS-CoV-2 / Sequence Homology / Severe acute respiratory syndrome coronavirus 2 / Severe acute respiratory syndrome-related coronavirus / Stat1 protein / STAT1 Transcription Factor / STAT1 Transcription Factor - metabolism / Strains (organisms) / therapeutics / Viral Nonstructural Proteins / Viral Nonstructural Proteins - genetics / Viral Nonstructural Proteins - metabolism / Virology / Virulence / viruses