Could a unique new fungus offer an opioid alternative?
A new fungus discovered in the estuarine waters of Tasmania could be the unexpected answer to the world’s opioid crisis, a current study suggests.
Opioids — many of which are prescription painkillers, such as codeine — have created a worldwide health crisis. Many opioids are highly addictive substances that some people overuse or misuse.
According to data from the National Institute on Drug Abuse, over 130 people die each day in the United States because of an opioid overdose.
The Health Resources and Services Administration call this “an unprecedented opioid epidemic.” The situation has led to the World Health Organization (WHO) encouraging countries to monitor the use of opioid drugs closely.
But while monitoring the use of opioids is helpful, scientists are on the lookout for opioid alternatives. They are searching for drugs that will treat chronic pain in the same way as opioids but are less likely to harm health or lead to misuse.
A novel discovery by researchers from the University of Sydney in Australia — in collaboration with colleagues from other academic institutions — may, in the future, lead to the development of one such potent alternative.
The team found an unknown species of the fungus Penicillium in an estuary in the Huon Valley in Tasmania. The researchers showed that this fungus contained a set of molecules called “tetrapeptides,” which are amino acids.
These molecules had a unique structure that emulates the shape of endomorphins, which are natural opioid chemical messengers that help deliver pain relief.
The team notes that these new fungus-derived tetrapeptides have the potential to cause fewer side effects than regular opioids, while still delivering effective pain relief.
A ‘never-before-seen’ molecular structure
Senior author Prof. Macdonald Christie and colleagues explain that the newly discovered fungus yielded three different versions of tetrapeptides — with a very interesting and unexpected molecular structure.
More specifically, the team found that these fungus-derived molecules had a surprising chirality, or “handedness,” which refers to the geometric orientation of the molecular structure.
Some molecules have a geometric property that means they can have a “left handed” or a “right handed” structure, the two of which are mirror images of each other.
Moreover, their orientation can make a significant difference, since it will determine how a molecule “fits” or reacts with other molecules that it interacts with.
In nature, most amino acids display “left handedness,” and while there are some exceptions, the amino acids present in mammals are very rarely “right handed.”
This is important because, as the researchers explain in their paper — which appears in the journal PNAS — recent studies have emphasized the importance of peptides (short-chain amino acids) of mammalian origin in the context of developing new and better alternatives to traditional opioids.
The tetrapeptides present in the newly discovered Penicillium are special precisely because they display “right handedness.” This unusual chirality allowed the researchers to determine these molecules’ properties and the fact that they were a promising alternative to opiates.
“No one had ever pulled anything out of nature, anything more ancient than a vertebrate that seemed to act on opiate receptors — and we found it,” says Prof. Christie.
“The structure we found has never been seen before.”
Prof. Macdonald Christie
The team has already filed a patent application in Australia and continues the research, aiming to confirm whether the newly discovered molecules can lead to the development of a novel drug.
However, Prof. Christie cautions that even if they do get their confirmation and begin further tests, it could be another 10 years until the new pain reliever becomes commercially available.
Yet, he emphasizes, “[i]f this proves successful and leads to a new medication, it will significantly reduce the risk of death by overdose from opioid medications, such as codeine.”