Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 29 December 2020 / Approved: 30 December 2020 / Online: 30 December 2020 (09:42:41 CET)

How to cite: Díaz, J.; Álvarez-Buylla, E.R.; Bensussen, A. SARS-CoV-2 Nsp5 Protein Causes Acute Lung Inflammation: A Mathematical Model. Preprints 2020, 2020120749 (doi: 10.20944/preprints202012.0749.v1). Díaz, J.; Álvarez-Buylla, E.R.; Bensussen, A. SARS-CoV-2 Nsp5 Protein Causes Acute Lung Inflammation: A Mathematical Model. Preprints 2020, 2020120749 (doi: 10.20944/preprints202012.0749.v1).

Abstract

In the present work we propose a mathematical model of the process of inflammation in lung cells in response to SARS-CoV-2 infection from which a plausible scenario for the dynamics of this process arise. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kappaB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. When in presence of the virus the translation rates of NF kappaB and IkB are increased to a high constant value, and the translation rate of IL-6 is increased above the threshold value of 7 nM s-1, the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. This over stimulated immune state becomes autonomous of the signals from other immune cells like macrophages and lymphocytes, and does not shut down by itself. Dexamethasone or Nimesulide have little effect on this 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 with drugs like Saquinavir. In this form, our model suggests that Nsp5 is effectively the cause of 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. From an evolutive point of view, the use of Nsp5 as the switch to start inflammation, and the consequent overproduction of the ACE2 receptor, is the probable reason of the increased dangerousness of SARS-CoV-2 with respect to SARS-CoV.

Subject Areas

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

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