Catalase, a naturally occurring enzyme commonly used worldwide in food production and as a dietary supplement, holds potential as a low-cost therapeutic drug to treat the symptoms of the COVID-19 disease and suppress the replication of the SARS-CoV-2 virus inside the body.
Proposed mechanism of action and synthesis of catalase nanocapsules: (A) a schematic illustrating that an elevated level of reactive oxygen species (ROS) causes oxidative injury, promotes viral replication, and triggers cytokine storm syndrome in COVID-19 patients; (B) the reaction pathways of ROS, suggesting that eliminating hydrogen peroxide is the key to minimizing the formation of downstream ROS; (C) the synthesis of catalase nanocapsules by in situ polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) and N,N’-methylenebisacrylamide (BIS) around individual catalase molecules exhibiting improved stability and circulation half-life. Image credit: Qin et al, doi: 10.1002/adma.202004901.
Catalase is the most abundant antioxidant enzyme ubiquitously present in the liver, erythrocytes and alveolar epithelial cells.
Inside cells, it kick starts the breakdown of hydrogen peroxide (H2O2) into water and oxygen. One molecule of catalase can breakdown 10 million molecules of hydrogen peroxide in one second.
However, catalase generally exhibits poor stability and a short plasma half-life.
“There is a lot of focus on vaccines and antiviral drugs, and rightly so,” said senior author Professor Yunfeng Lu, a researcher in the Department of Chemical and Biomolecular Engineering, Microbiology, Immunology and Molecular Genetics, and the David Geffen School of Medicine at the University of California, Los Angeles.
“In the meantime, our research suggests this enzyme could offer a very effective therapeutic solution for treatment of hyperinflammation that occurs due to the SARS-CoV-2 virus, as well as hyperinflammation generally.”
To explore the therapeutic use of catalase, Professor Lu and colleagues carried out three types of tests, each addressing a different symptom of COVID-19.
First, the scientists demonstrated the enzyme’s anti-inflammatory effects and its ability to regulate the production of cytokines, a protein that is produced in white blood cells.
Cytokines are an important part of the human immune system, but they can also signal the immune system to attack the body’s own cells if too many are made — a so-called ‘cytokine storm’ that is reported in some patients diagnosed with COVID-19.
Second, the authors showed that catalase can protect alveolar cells, which line the human lungs, from damage due to oxidation.
Finally, in the experiments in rhesus macaques, they showed that catalase can repress the replication of the SARS-CoV-2 virus without noticeable toxicity.
“This work has far-reaching implications beyond the treatment of COVID-19,” said co-author Dr. Gregory Fishbein, also from the Department of Chemical and Biomolecular Engineering, Microbiology, Immunology and Molecular Genetics, and the David Geffen School of Medicine at the University of California, Los Angeles.
“Cytokine storm is a lethal condition that can complicate other infections, such as influenza, as well as non-infectious conditions, like autoimmune disease.”
The study was published in the journal Advanced Materials.
Meng Qin et al. An Antioxidant Enzyme Therapeutic for COVID-19. Advanced Materials, published online September 13, 2020; doi: 10.1002/adma.202004901
This article is based on a press-release provided by the University of California, Los Angeles.