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Updated: Jul 28, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis

Lihong Liu1, Jie Du2, Sidi Yang3

  • 1MOE Key Laboratory of Tropical Disease Control, Centre for Infection and Immunity Study (CIIS), School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, China; Guangzhou Laboratory, Bio-island, Guangzhou, Guangdong, PR China.

Redox Biology
|May 28, 2023
PubMed

Insights

The SARS-CoV-2 virus

Area of Science:

  • Virology
  • Cellular Biology
  • Immunology

Background:

  • Viral infection-induced cell death impacts viral pathogenesis.
  • Severe COVID-19 involves organ dysfunction and cytokine storms, potentially linked to SARS-CoV-2-induced cell death.
  • Elevated reactive oxygen species (ROS) and ferroptosis signs are noted in COVID-19, but mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the mechanism by which SARS-CoV-2 induces cell death.
  • To investigate the role of the SARS-CoV-2 ORF3a protein in cell death pathways.
  • To explore the connection between SARS-CoV-2 infection, oxidative stress, and ferroptosis.

Main Methods:

  • Investigated the interaction between SARS-CoV-2 ORF3a and the Keap1-NRF2 pathway.
  • Assessed the impact of ORF3a on NRF2 degradation and cellular oxidative stress resistance.
  • Utilized cell models to study ferroptosis induction by SARS-CoV-2 components.

Main Results:

  • SARS-CoV-2 ORF3a sensitizes cells to ferroptosis.
  • ORF3a promotes NRF2 degradation by recruiting Keap1, reducing cellular antioxidant defense.
  • This mechanism facilitates ferroptotic cell death, contributing to viral pathogenesis.

Conclusions:

  • SARS-CoV-2 ORF3a acts as a positive regulator of ferroptosis.
  • This finding may explain multi-organ damage observed in COVID-19 patients.
  • Inhibition of ferroptosis presents a potential therapeutic strategy for COVID-19.
Keywords:
FerroptosisKeap1NRF2ORF3aSARS-CoV-2

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