Related Experiment Video
Updated: Jun 5, 2026
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
Summary
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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