Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Likely Role of de-Mono-ADP-ribosylation of STAT1 by the SARS-CoV-2 nsp3 Protein in the Cytokine Storm Syndrome of COVID-19

Version 1 : Received: 8 May 2020 / Approved: 11 May 2020 / Online: 11 May 2020 (13:11:43 CEST)

How to cite: Claverie, J. The Likely Role of de-Mono-ADP-ribosylation of STAT1 by the SARS-CoV-2 nsp3 Protein in the Cytokine Storm Syndrome of COVID-19. Preprints 2020, 2020050198 (doi: 10.20944/preprints202005.0198.v1). Claverie, J. The Likely Role of de-Mono-ADP-ribosylation of STAT1 by the SARS-CoV-2 nsp3 Protein in the Cytokine Storm Syndrome of COVID-19. Preprints 2020, 2020050198 (doi: 10.20944/preprints202005.0198.v1).

Abstract

As more cases of COVID-19 are studied and treated world-wide, it had become apparent that lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the SARS-CoV2 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 point out de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a likely cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and an assay to predict the virulence of naturally circulating SARS-like animal coronaviruses.

Subject Areas

de-MARylation; interferon-stimulated gene; inflammation; PARP14; ACE2; coronavirus

Comments (1)

Comment 1
Received: 16 June 2020
Commenter: Jean-Michel Claverie
The commenter has declared there is no conflict of interests.
Comment: The final version of this article is now published as: J-M. Claverie. (2020) 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 Viruses 2020, 12, 646; doi:10.3390/v12060646
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