Finding new therapeutics in fungi

The recent hit HBO series The Last of Us(在新的选项卡/窗口中打开) — a post-apocalyptic story in which the planet has been ravaged by a terrifying fungal infection — has some people re-thinking their affection for mushrooms. But while fungi can have their downsides, they have long been not only a source of sustenance but of healing. Fungi have been used in traditional medicines for ages and eventually went on to become the source of that modern miracle: penicillin.

Fungi are brimming with potential. They are full of natural compounds that help them adapt to their environment, survive and thrive. Still, the vast majority of compounds within fungi remain a mystery to scientists.

“Fungi can encode up to approximately a hundred different natural products in their genomes, but they only seem to express a small percentage of them at any given time,” writes Stephanie DeMarco, PhD(在新的选项卡/窗口中打开), in Drug Discovery News(在新的选项卡/窗口中打开). “Scientists are developing computational approaches to identify lowly expressed or silent fungal natural products to discover new potential therapeutic molecules for maladies as diverse as infectious diseases and cancer.”

Re-discovering the power of fungi with new approaches

Unlocking the compounds in fungi could lead to creating new therapeutics, but making the process more efficient is critical. For decades, many drug developers have calculated that this development path is too time-consuming, so current efforts are largely focused on developing technology and techniques to speed up the process.

GSK invests in a promising start-up

The belief that fungi could be a still largely untapped resource for new drugs may be gaining steam in the industry. Last year, GlaxoSmithKline joined with other investors to fund LifeMine Therapeutics(在新的选项卡/窗口中打开), a biotech start-up that wants to use fungi to fight cancer, demonstrating that large companies think there might be a therapeutic goldmine hiding in the fungus.

“LifeMine has developed a proprietary platform that employs high throughput biology, artificial intelligence and other technologies to search for the molecules that have a target and a biological function that could have application in humans as a drug,” reported Frank Vinluan in MedCityNews(在新的选项卡/窗口中打开) about the new company’s endeavors. LifeMine’s approach is to sidestep searching through molecules and instead search fungal genes to point them in the right direction.

A new chemo drug goes to trials

Although most of the work related to fungi right now is focused on unleashing its potential, there are some researchers finding success further down the pipeline. Oxford University and biopharma NuCana recently partnered on a study of chemotherapy drug NUC-7738(在新的选项卡/窗口中打开), finding that it’s up to 40 times as potent as its parent compound Cordycepin, found in the Himalayan fungus Cordyceps sinensis. While Cordycepin has long been used in traditional medicine, it normally breaks down quickly in the bloodstream, diluting its effectiveness. NuCana has developed it as a chemotherapy drug using a novel technology, and now the study has proved its potency. Phase 2 clinical trials are in the works.

Resources for researchers focused on fungi

Better tools and resources are always needed to help scientists work more efficiently and effectively. Hubrecht Institute(在新的选项卡/窗口中打开) researchers have been collaborating with Westerdijk Fungal Biodiversity Institute(在新的选项卡/窗口中打开), which houses the largest collection of live fungi in the world, to create a vast library of natural products derived from over 10,000 fungi(在新的选项卡/窗口中打开). They have already tested the biological activity of these products using zebrafish embryos, leading to them finding over 1,500 filtrates containing biologically active compounds with an effect on the embryos, and eventually isolating 34 known compounds.

These results are just the beginning, and the library stands to be an important resource for other researchers. “The large library of fungal filtrates that we have set up can also be tested in many other systems, such as models for antibiotic resistance in bacteria and tumor development, making this study only the tip of the iceberg,” said Jelmer Hoeksma of the Hubrecht Institute.