Opioid Alternative: New Fungus Could Provide Safe Option

Australian researchers have found that a previously unknown species of the fungus Penicillium, the same species that gives us penicillin, shows promise as an effective and safe opioid alternative.

What's being described as a novel and potentially beneficial discovery by researchers from the University of Sydney (USyd) in Australia, along with colleagues from other academic institutions, could lead to the development of a potent alternative to opioids. The abuse and misuse of opioids has led to a lethal opioid epidemic in the United States that kills some 130 persons daily.

The United States consumes 80 percent of the global pharmaceutical opioid supply. Canada is the next most impacted country by opioids.

There is a valid concern among health professionals that drug companies making opioids might target more countries as they sell their opioid products, transforming the opioid epidemic into a global pandemic.

The USyd team found this unknown fungus Penicillium species in an estuary in the Huon Valley in Tasmania. Their research discovered this fungus has a set of molecules called "tetrapeptides" whose unique structure emulates the shape of endomorphins, which are natural opioid chemical messengers that help deliver pain relief. Tetrapeptides are amino acids.

The researchers also said these new fungus-derived tetrapeptides have the potential to cause fewer side effects than regular opioids, but will deliver effective pain relief. The newly discovered fungus yielded three different versions of tetrapeptides.

These versions have a very interesting and unexpected molecular structure, according to study senior author Prof. Macdonald Christie. The team found these fungus-derived molecules had a surprising "chirality," also called "handedness."

This 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. These two are mirror images of each other. Their orientation can make a significant difference since it will determine how a molecule reacts or "fits" with other molecules it interacts with.

In nature, most amino acids display "left handedness." Amino acids present in mammals are rarely "right handed."

Researchers said handedness is important because recent studies have emphasized the importance of peptides (or 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 because they display "right handedness." This unusual chirality allowed researchers to uncover these molecules' properties, and 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," said Prof. Christie. “The structure we found has never been seen before."

The team has filed a patent application in Australia and continues their research. They seek to confirm if the newly discovered molecules can lead to the development of a novel opioid drug.