A wild fungus could help doctors produce a safer class of opioid drugs

"Microbes may be an untapped resource."


Despite the risks of overdose and [addiction]( that come with opioid pain relievers, doctors still haven’t found a better class of medicine to treat pain. As the opioid overdose crisis claims tens of thousands of lives a year in the United States, though, and doctors have become increasingly cautious about prescribing opioids to people who need them, new research is focusing on developing opioid drugs that won’t come with the same dangers of accidental overdose of accidental overdose as conventional ones like morphine, oxycodone, or fentanyl.

And a study out this week indicates that researchers have come one step closer to developing opioids with fewer dadangerous side effects.

A team in Australia investigated a specific species of Penicillium fungus that grows in the country’s estuaries and found that it can be used to produce an opioid with properties that could make it dedesirable for use as a medication. The team outlined its findings in a study published on Monday in the journal Proceedings of the National Academy of Sciences. In the paper, the investigators outline why they wanted to pursue an alternative to opioid analgesics — the scientific name for pain relievers.

“Notwithstanding their value in alleviating pain, serious adverse side effects, combined with the challenge of addiction, abuse, and acquired tolerance, render these analgesics (particularly opioids) far from ideal,” they write. “There is an urgent need to discover and develop new, safer and more efficacious analgesics, with mechanisms of actions that mitigate against risk.”

The new compound called bilorphin (red) bound to a mu opioid receptor (tan). 

Image courtesy of Richard B. Sessions

And in an effort to develop these safer versions of opioid analgesics, the team looked to a fungus from the same genus as the one we get the antibiotic penicillin from.

The team isolated three different molecules called tetrapeptides from the fungus called Penicillium sp. MST-MF667 and examined their unique structures. Recognizing that the tetrapeptides closely resembled existing opioid molecules — called μ-opioid agonists,, because they bind to the μ-opioid receptors — the investigators designed a new opioid molecule using the tetrapeptides as inspiration. They named this substance “bilorphin.”

Their iTheir investigations revealed that it wouldn’t be active without some chemical tweaks, so they performed them, creating another new molecule. They then tested this substance, which they named “bilactorphin,” in a computerized simulation to determine how it would most likely interact with μ-opioid receptors and the other related cell signaling pathways in living creatures. What they saw was that the substance seems like it will bind with μ-opioid receptors much like morphine and other conventional opioids do, but with a major difference.

Chemical structure of bilorphin tetrapeptide.

Image courtesy of Richard B. Sessions

Typical opioid analgesics bind to opioid receptors by recruiting a protein called β-arrestin. This sends out chemical signals that can result in the most dangerous side effect of opioid analgesic drugs: respiratory depression — which can eventually lead to death in what is commonly known as an overdose. But bilorphactin doesn’t recruit β-arrestin, so the team behind the study suspects it could be just as effective at managing pain as morphine, all without the potential for accidental overdose.

This study just describes one of the earliest efforts to unravel this molecule, but the researchers are optimistic about what their future efforts will yield.

“This observation suggests that microbes may be an untapped resource for new analgesics, deserving of further investigation,” they write.

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