Endoplasmic reticulum stress and NF-kB activation in SARS-CoV-2 infected cells and their response to antiviral

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Desirée Bartolini1,2, Anna Maria Stabile2, Carmine Vacca1

  • 1Department of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, Italy.

IUBMB Life
|August 14, 2021
PubMed

Insights

SARS-CoV-2 infection activates the unfolded protein response (UPR) and NF-kB pathway, promoting inflammation. Nelfinavir treatment reversed these effects, highlighting potential therapeutic targets for COVID-19.

Area of Science:

  • Cellular biology
  • Virology
  • Immunology

Background:

  • SARS-CoV-2 infection involves host cell interactions, including unfolded protein response (UPR) and endoplasmic reticulum (ER) stress.
  • The role of the NF-kB pathway in SARS-CoV-2 pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the interplay between SARS-CoV-2, UPR, NF-kB signaling, and MAPK pathways.
  • To explore the therapeutic potential of inhibiting viral replication on these cellular responses.

Main Methods:

  • Analysis of NF-kB protein expression and activity in SARS-CoV-2 infected VERO-E6 cells.
  • Assessment of MAPK signaling, IRE-1α expression, and caspase activation.
  • Evaluation of Nelfinavir's effect on viral replication and associated molecular changes.

Main Results:

  • SARS-CoV-2 infection significantly upregulated NF-kB activity early in the infection process.
  • Activated NF-kB was linked to increased MAPK signaling and IRE-1α expression, indicating cellular stress.
  • Nelfinavir inhibited viral replication, reverted molecular changes, and promoted anti-inflammatory c-Jun expression.

Conclusions:

  • SARS-CoV-2 infection triggers UPR and NF-kB signaling, contributing to a pro-inflammatory host response.
  • The interaction between UPR, MAPKs, and NF-kB is crucial in SARS-CoV-2 pathogenesis.
  • Targeting these pathways, as demonstrated by Nelfinavir, may offer therapeutic strategies for COVID-19.
Keywords:
COVID-19NF-kBNelfinavirRemdesivirSARS-CoV-2VERO-E6 cellsc-Juninflammationstress response

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