Researchers have potentially unlocked a remarkable new therapy for a sickness that has been the bane of firefighters and first responders for as long as anyone can remember: carbon monoxide poisoning.
A collaborative team from the University of Pittsburgh and the University of Maryland School of Medicine has developed a novel therapy for the poison; the team engineered it from a natural protein found in the bacterium Paraburkholderia xenovorans. This hemoprotein, RcoM-HBD-CCC, effectively acts as a sponge, scavenging carbon monoxide from the blood (Proc. Natl. Acad. Sci. U.S.A. 2025, DOI: 10.1073/pnas.2501389122).
Tens of thousands die from CO poisoning worldwide each year, in addition to millions more nonfatal incidents. The odorless gas can wreak such havoc because it binds to hemoglobin with hundreds of times the efficiency of oxygen and because its slowly escalating symptoms of hypoxia—from headache and nausea to dizziness to dyspnea and confusion—can sneak up on unsuspecting victims until it’s too late.
An illustration of multiple, twisting, cyan-colored ribbons connected by thin strands, surrounding an assemblage of tiny spheres representing various molecules.
This image depicts the CO sponge RcoM-HBD-CCC as generated in AlphaFold, with Heme and Histidine 74 (residue providing the covalent bond between the protein and the heme) as balls and sticks. Carbon atoms are marked as green, nitrogen as blue, iron as orange, and oxygen as red.
Credit:
Jesus Tejero
But to date, the only treatment for CO poisoning has been oxygen itself, sometimes just room air, other times 100% oxygen or—in extreme cases, such as with pregnant people—hyperbaric chambers. But each of those routes requires valuable time to slowly and steadily flush CO from the body. In emergency medicine, which calls the critical period after a person’s trauma the golden hour (or even the platinum ten minutes), such interventions can feel excruciatingly slow.
By contrast, this novel protein therapy can flush half the CO from the body in less than a minute. RcoM-HBD-CCC originates from RcoM (short for regulator of CO metabolism), a sensor protein that can detect CO down to the nanomolar level. And by using stopped-flow electronic absorption spectroscopy, the researchers found that RcoM-HBD-CCC binds CO nearly 50 times as fast as hemoglobin binds CO, such that it works as soon as it hits the bloodstream.
RcoM-HBD-CCC isn’t the first candidate for a CO-poisoning antidote. One of the field’s enduring challenges, however, has been to find a scavenger that doesn’t also possess an affinity for nitric oxide, which serves as a critical regulator of blood pressure. It would be a superb irony to avert a case of CO poisoning only to manifest debilitating hypertension. Importantly, the researchers note that intravenous administration of RcoM-HBD-CCC in mice did not exhibit any hypertensive effects.
Timothy Johnstone, who is a guest editor for the paper and whose lab at the University of California, Santa Cruz, has been working to develop its own solution to the problem using small-molecule iron-porphyrin complexes, has high hopes for the therapy’s future. “This is a problem so uniquely suited to a bioinorganic solution,” Johnstone says. “Technical improvements like the one described here will only continue to bring the application closer to practical realization.”
On top of its promising future as an antidote, RcoM-HBD-CCC has properties that could also serve as the foundation for other novel means of oxygen delivery, treatments for blood loss and anemia, or even preservation of organs for transplantation. Developers now hope to scale up production and prepare for clinical trials.
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