The COVID-19 pandemic may have its zoonotic origins in bats, but it seems rattlesnake venom is also at play.
In new research, scientists have identified a specific enzyme—sPLA2-IIA—that may be a key mechanism driving COVID-19 severity and mortality. Known for its elusive role in severe inflammation in the human body, sPLA2-IIA bears similarities to an enzyme found in rattlesnake venom.
“The 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," explains Floyd (Ski) Chilton, senior author on the paper and director of the UArizona Precision Nutrition and Wellness Initiative.
In low concentrations in healthy individuals, sPLA2-IIA actually plays a critical role destroying microbial cell membranes during bacterial infections. However, when the enzyme circulates at high levels, researchers say it has the capacity to shred the membranes of vital organs.
"It's a bell-shaped curve of disease resistance versus host tolerance," said Chilton. "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."
Working with colleagues at the University of Arizona, Stony Brook University and Wake Forest University, Chilton analyzed blood samples from two COVID-19 patient cohorts to shed light on how a a potential prognostic factor in COVID-19 patients.
First, SUNY professor Maurizio Del Poeta and his team tracked down clinical data and medical charts for 127 patients hospitalized at Stony Brook University in New York between January and July 2020. The second cohort included a mix of 154 patient samples collected from Stony Brook and Banner University Medical Center in Arizona between January and November 2020.
Using machine learning algorithms, the researchers focused on biochemical enzymes and lipid metabolites, searching for patterns present in patients who ultimately succumbed to COVID-19.
According to the study, published in the Journal of Clinical Investigation, the metabolites that stuck out were characterized by cell energy dysfunction and high levels of the sPLA2-IIA enzyme—the latter something the team says they did not expect. While most healthy individuals have levels of sPLA2-IIA hovering around 0.5 ng/mL, the study revealed COVID-19 was fatal in 63% of patients who had sPLA2-IIA levels equal to or greater than 10 ng/mL.
"Many patients who died from COVID-19 had some of the highest levels of this enzyme that have ever been reported," said Chilton, who has been studying the enzyme for over three decades.
Del Poeta says their study, together with clinically tested sPLA2-IIA inhibitors, supports a new therapeutic target to reduce or even prevent COVID-19 mortality. To that end, the research team plans to continue working to better understand how sPLA2-IIA affects patients with COVID-19—and how they can exploit the enzyme in the future.
"Roughly a third of people develop long COVID, and many of them were active individuals who now can't walk 100 yards. 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?,” concluded Chilton.