COVID-19 kills patients using an enzyme similar to neurotoxins in rattlesnake venom

TUCSON, Ariz. — COVID-19 appears to kill patients in the same way a rattlesnake does — triggering a protein related to neurotoxins found in the reptile’s venom, a new study reveals. Scientists at the University of Arizona believe the mechanism may hold the key to predicting patients most likely to die from the virus.

This trigger fuels the severity of the virus by causing severe inflammation. A patient’s immune system goes into overdrive, leading to organ failure.

“Many patients who died from COVID-19 had some of the highest levels of this enzyme that have ever been reported,” says study senior author Dr. Floyd Chilton in a university release.

The COVID enzyme shares the same genetic ancestry as the key active chemical in snake venom.

Dr. Chilton add that this protein “shares a high sequence homology to the active enzyme in rattlesnake venom and, like venom coursing through the body, it has the capacity to bind to receptors at neuromuscular junctions and potentially disable the function of these muscles.”

Could snake venom similarities explain ‘long COVID’?

Neurotoxins from a rattlesnake bite can kill a human within a couple of hours. The shock discovery could also shed light on long-COVID, which continues to cause symptoms weeks or months after infection. Those symptoms range from fatigue, headaches, and breathlessness, to fever and stomach pain.

“Roughly a third of people develop long COVID, and many of them were active individuals who now can’t walk 100 yards,” the study author continues. “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?”

The study, published in the Journal of Clinical Investigation, opens the door to a fresh therapeutic to reduce COVID mortality rates. Their findings come from an analysis of blood samples from two groups of COVID-19 patients. Experts say vaccines alone will not conquer the pandemic. However, the world is still waiting for an effective anti-viral drug to enter circulation.

Dr. Chilton has been investigating the protein, called sPLA2-IIA (secreted phospholipase A2 group IIA), for more than three decades. It has also been the subject of studies for half a century. The Arizona team notes that the protein has “similarities to an active enzyme in rattlesnake venom.”

Healthy people actually carry this protein

Surprisingly, the protein is also found in low concentrations in healthy individuals, playing a critical role in fighting infections by destroying bacteria. At high levels however, it “shreds” the membranes of vital organs.

“It’s a bell-shaped curve of disease resistance versus host tolerance,” Dr. Chilton explains. “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, destroying the patient’s cell membranes and thereby contributing to multiple organ failure and death.”

Medications which act as sPLA2-IIA inhibitors are already undergoing tests during the pandemic.

“The study supports a new therapeutic target to reduce or even prevent COVID-19 mortality,” adds co-author Professor Maurizio Del Poeta of Stony Brook University.

Dr. Chilton contacted Del Poeta last year with the idea to identify a potential prognostic factor in the blood lipids (or fats) and metabolites of patients. Prof. Del Poeta and colleagues collected stored plasma samples, looked at medical charts, and tracked down clinical data from 127 of their patients. A second independent study included a mix of 154 patient samples collected from Stony Brook and Banner University Medical Centre in Tucson, Arizona.

“These are small cohorts, admittedly, but it was a heroic effort to get them and all associated clinical parameters from each patient under these circumstances,” Dr. Chilton says. “As opposed to most studies that are well planned out over the course of years, this was happening in real time on the ICU floor.”

Determining the lethal dose of ‘COVID venom’

The researchers used AI (artificial intelligence) to analyze thousands of patient data points. They focused on biochemical enzymes and levels of lipid metabolites, as well as taking into account other risk factors including age, body mass index, and pre-existing health conditions.

“We were able to identify patterns of metabolites that were present in individuals who succumbed to the disease,” reports lead author Dr. Justin Snider from the University of Arizona. “The metabolites that surfaced revealed cell energy dysfunction and high levels of the sPLA2-IIA enzyme. The former was expected but not the latter.”

The machine learning algorithms showed most healthy individuals have circulating levels hovering around half a nanogram per milliliter. The virus was lethal in 63 percent of patients who had severe COVID and sPLA2-IIA levels of at least 10 nanograms per milliliter.

Prof. Charles McCall of Wake Forest University describes it as a “shredder” for its prevalence in serious inflammation such as bacterial sepsis and hemorrhagic and cardiac shock. To date, over 600,000 Americans have died from COVID-19 since the beginning of 2020.

Rattlesnakes are among the world’s most deadly predators. There are more than two dozen species. All have the iconic rattle at the tip of their tail to warn potential aggressors to back off – or to distract prey. Their venom from a bite will affect a victim’s circulatory system by destroying skin tissues and blood cells and by causing internal hemorrhaging.

South West News Service writer Mark Waghorn contributed to this report.