Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 01, 2026 38 minutes ago
Scientists have uncovered a troubling new way that SARS-CoV-2, the virus behind COVID-19, damages human cells. A new study has revealed that one of the virus's lesser-known proteins, called ORF7a, can severely disrupt the mitochondria—the tiny structures inside cells that generate energy. The discovery helps explain how COVID-19 can interfere with normal cell function and may also shed light on the lingering health problems experienced by many people after infection.
Scientists discover that the SARS-CoV-2 ORF7a protein disrupts mitochondria, reducing cellular energy production
while increasing oxidative stress
The research was conducted by scientists from the University of Córdoba, the Maimónides Biomedical Research Institute of Córdoba (IMIBIC), the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), the CIBER-CIBERFES, Instituto Carlos III, the Margarita Salas Center for Biological Research (CIB-CSIC), the National Institute for Aerospace Technology (INTA), and Reina Sofía University Hospital, all in Spain.
ORF7a Pushes Cells into Survival Mode
Instead of allowing cells to efficiently produce energy through their mitochondria, ORF7a forces them to rely more heavily on glycolysis, a faster but far less efficient method of generating energy. This metabolic switch is similar to what is often seen in cancer cells and in tissues under severe stress.
The researchers found that ORF7a boosted the production of proteins involved in glycolysis while reducing the cell's ability to burn pyruvate inside mitochondria. At the same time, the viral protein altered fat metabolism, nucleotide production and antioxidant systems, creating widespread metabolic disruption throughout the cell.
Mitochondria Lose Their Ability to Produce Energy
One of the study's most striking findings was that ORF7a dramatically reduced mitochondrial performance. Cells expressing the viral protein showed lower basal respiration, reduced ATP production, decreased maximum respiratory capacity and a much smaller energy reserve available during times of stress.
Although the mitochondria still appeared structurally normal under electron microscopy, they were functionally impaired. The researchers found a much larger proportion of low-activity mitochondria, indicating that the virus damages mitochondrial performance long before obvious physical damage becomes visible. This suggests that COVID-19 may silently weaken cellular energy production even when mitochondria appear intact.
Oxidative Stress Rises as Natural Defenses Fall
This
Medical News report highlights another major concern uncovered by the study. ORF7a significantly increased the production of harmful reactive oxygen species, commonly known as oxidative stress. At the same time, important antioxidant molecules including glutathione were depleted, leaving cells with fewer defenses against ongoing damage.
The investigators also observed changes in several antioxidant enzymes, suggesting that infected cells
attempted to compensate but were unable to fully restore normal redox balance. Excessive oxidative stress has already been linked to inflammation, tissue injury and many complications seen during COVID-19.
A Key Enzyme Is Switched Off
The researchers discovered that ORF7a greatly increased production of an enzyme called PDK4, which shuts down another critical enzyme complex responsible for moving pyruvate into the mitochondria to produce energy.
As PDK4 activity increased, pyruvate oxidation declined and cellular metabolism became increasingly dependent on glycolysis. Interestingly, even when researchers blocked PDK4 using the drug dichloroacetate, mitochondrial function failed to recover. This revealed that ORF7a causes damage through more than one mechanism.
Complex I Emerges as the Main Target
Further investigation identified the virus's primary target. ORF7a selectively impaired mitochondrial Complex I, one of the most important components of the cell's energy-producing machinery.
Complex I activity dropped significantly, while Complex II and Complex IV continued to function normally. The study also showed that ORF7a disrupted the assembly of respiratory supercomplexes, large molecular structures that allow mitochondria to produce energy efficiently. Without properly assembled supercomplexes, electron transport becomes inefficient, ATP production falls and oxidative stress increases even further.
Conclusions
The findings reveal that ORF7a is far more than a minor accessory protein. It acts as a powerful metabolic regulator that redirects cellular energy production, weakens mitochondrial function, increases oxidative stress and selectively disables Complex I while destabilizing respiratory supercomplexes. These discoveries provide important new insight into how SARS-CoV-2 damages cells and may help explain persistent metabolic abnormalities seen in some COVID-19 patients. The results also identify mitochondrial metabolism and ORF7a-driven pathways as promising targets for future therapeutic strategies aimed at reducing both acute disease severity and long-term complications.
The study findings were published in the peer reviewed journal: Cell Reports.
https://www.sciencedirect.com/science/article/pii/S2211124726008338
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