Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

SARS-CoV-2 Nsp5 Protein Causes Acute Lung Inflammation: A Dynamical Mathematical Model

Version 1 : Received: 29 December 2020 / Approved: 30 December 2020 / Online: 30 December 2020 (09:42:41 CET)
Version 2 : Received: 13 March 2021 / Approved: 15 March 2021 / Online: 15 March 2021 (12:18:02 CET)

How to cite: Díaz, J.; Álvarez-Buylla, E.R.; Bensussen, A. SARS-CoV-2 Nsp5 Protein Causes Acute Lung Inflammation: A Dynamical Mathematical Model. Preprints 2020, 2020120749 (doi: 10.20944/preprints202012.0749.v2). Díaz, J.; Álvarez-Buylla, E.R.; Bensussen, A. SARS-CoV-2 Nsp5 Protein Causes Acute Lung Inflammation: A Dynamical Mathematical Model. Preprints 2020, 2020120749 (doi: 10.20944/preprints202012.0749.v2).

Abstract

In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 also increases above the threshold value of 7 pg mL-1 s-1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5.To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 is effectively a central node underlying the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. Nsp5 seems to be the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.

Subject Areas

SARS-CoV-2 infection; Interleukin 6; NFB; Nsp5; Cox2; SARS-CoV-2 interactome; Nonlinear dynamics of inflammation

Comments (1)

Comment 1
Received: 15 March 2021
Commenter: José Díaz
Commenter's Conflict of Interests: Author
Comment: The content of the article has been reviewed, corrected and updated. New material has been added Supplementary material 2. Concentration units in all Figures were corrected.
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