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Updated: Jun 5, 2026

Oxygen-Independent Assays to Measure Mitochondrial Function in Mammals
05:59

Oxygen-Independent Assays to Measure Mitochondrial Function in Mammals

Published on: May 19, 2023

Mitochondrial OXPHOS restricts SARS-CoV-2 replication

Yentli E Soto Albrecht1,2,3,4, Ryan M Morrow1, Devin Kenney3,4

  • 1Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Science Advances
|June 3, 2026
PubMed

Insights

Mitochondrial oxidative phosphorylation (OXPHOS) inhibits SARS-CoV-2 replication. Inhibiting OXPHOS boosts viral production, while restoring it reduces virus levels, highlighting metabolic balance in controlling infection.

Area of Science:

  • Virology
  • Cell Biology
  • Metabolic Research

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manipulates host cell metabolism for replication.
  • The role of mitochondrial oxidative phosphorylation (OXPHOS) in SARS-CoV-2 production remains unclear.
  • Mitochondrial DNA (mtDNA) encodes essential components for OXPHOS and mitochondrial protein synthesis.

Purpose of the Study:

  • To investigate the impact of OXPHOS on SARS-CoV-2 replication.
  • To determine if OXPHOS inhibition affects viral production and replication dynamics.
  • To elucidate the role of metabolic balance in regulating SARS-CoV-2 infection.

Main Methods:

  • Utilized human ACE2-expressing A549 lung cells, including mtDNA-depleted (ρ0) cells.
  • Inhibited OXPHOS using mtDNA depletion, chloramphenicol (CAP), and chemical inhibitors.
  • Assessed viral production, replication center formation, and infectious particle release.
  • Analyzed glycolytic capacity and innate immune pathway activation.
  • Restored OXPHOS by reintroducing mtDNA into ρ0 cells.

Main Results:

  • SARS-CoV-2 production increased 5- to 100-fold upon OXPHOS inhibition.
  • OXPHOS inhibition accelerated viral replication and particle release by approximately 2 hours.
  • Enhanced viral replication correlated with increased glycolytic capacity, not innate immunity.
  • Restoring OXPHOS impaired viral replication and reversed metabolic changes.

Conclusions:

  • Mitochondrial oxidative phosphorylation (OXPHOS) exerts an antiviral effect against SARS-CoV-2.
  • Metabolic balance, specifically the interplay between OXPHOS and glycolysis, is critical for regulating viral replication.
  • Targeting OXPHOS could be a potential strategy for managing SARS-CoV-2 infection.

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