The link between COVID-19, rattlesnake venom and a killer enzyme inspires treatment target

University of Arizona Professor Floyd (Ski) Chilton, Ph.D., has been studying an enzyme related to rattlesnake venom for 30-plus years. Now, he has evidence that the enzyme could drive severe forms of COVID-19—and provide a new target for reducing mortality from the virus.

Chilton’s team worked with researchers at Stony Brook University and Wake Forest University School of Medicine to study blood samples from 281 COVID patients. They discovered that levels of the enzyme secreted phospholipase A2 group IIA (sPLA2-IIA) could predict which patients were likely to succumb to the disease, they reported in the Journal of Clinical Investigation.

The enzyme is similar to an enzyme in rattlesnake venom that can bind to receptors in muscles and paralyze them. In people, sPLA2-IIA normally occurs at low levels and is perfectly safe—in fact, it actually protects against infections by destroying the cell membranes of microbes. But in high quantities, it can “shred” vital organs, Chilton explained in a statement.

"In other words, this enzyme is trying to kill the virus, but at a certain point it is released in such high amounts that things head in a really bad direction,” Chilton said.

RELATED: Diabetes mainstay metformin tamps down lung inflammation in COVID models

The University of Arizona-led team analyzed samples from COVID patients using machine learning algorithms that wrapped together risk factors like age and body mass index with circulating levels of lipids and enzymes. The researchers discovered that people with severe COVID had signs of dysfunctional cellular energy, which they expected. But they were surprised to find high levels of sPLA2-IIA.

Tamping down out-of-control inflammation from COVID is a major focus of ongoing research. In June, researchers led by the University of California, San Diego published research showing the diabetes drug metformin slowed the onset of severe lung inflammation in mouse models. The researchers explained that the drug prevents the activation of a key inflammatory pathway in the immune system.

Indian researchers recently proposed using the tuberculosis vaccine Bacillus Calmette-Guérin (BCG) to control inflammation in some COVID patients, and an Australian team discovered beneficial gut bacteria that could protect against lung inflammation in mice.

Chilton’s team suggested further research could inspire ideas for pursuing sPLA2-IIA as a therapeutic target in COVID-19.

"Roughly a third of people develop long COVID, and many of them were active individuals who now can't walk 100 yards,” Chilton said. “The question we are investigating now is: If this enzyme is still relatively high and active, could it be responsible for part of the long COVID outcomes that we're seeing?”