Working on a sample of estuarine mud, collected next to a boat ramp in Tasmania 16 years ago, as part of an effort to study the chemistry of marine Penicillium fungi, Professor Rob Capon from the University of Queensland (UQ) and his team have found a potential replacement for the widely used – and highly addictive – opioid drugs.

“We came across a fungus that yielded a new type of molecule which we named the bilaids, that I noticed were similar to endomorphins – natural peptides produced by the human body that activate opioid receptors and provide pain relief,” Capon said.

Together with colleagues from UQ and the University of Sydney (US), Capon then modified the new-found molecule to produce a substance dubbed bilorphin which proved to be as potent as morphine, but much less destructive to the human body.

“No one ever pulled anything out of nature, anything more ancient than a vertebrate, that seemed to act on opioid receptors – and we found it. If 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,” explained study co-author Professor Macdonald Christie from US.

The principal reason why the new molecule is so powerful has to do with its “handedness” – while most natural molecules are “left-handed” in terms of their amino acid composition, bilaids are unique in featuring both “left-handed” and “right-handed” patterns of amino acids.

This is important because opioids such as morphine activate a signalling cascade (one of two) sent by opioid receptors, which is hypothesised to be responsible for the negative effects of these drugs. In contrast, bilaids – and especially the bilaid-derived bilorphin – activate receptors with the opposite bias and could therefore be a far safer alternative to currently available painkillers.

According to Capon, the discovery is valuable not only because of its more straightforward pharmaceutical applications, but also because it might serve as further encouragement for researchers to keep investigating the soil and its native microbial and fungal populations for new and superior drugs.

“Although our discovery of an analgesic from an estuarine mud fungus was serendipitous, it does beg the question – with an almost infinite diversity of fungi in the soils, plants, animals and waters of the planet, perhaps we should be exploring other fungi for analgesics?,” said Capon.

Source: imb.uq.au, research paper