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Finding new therapeutics in fungi

2024年4月10日

Ann-Marie Roche

Computer illustration of fruiting bodies (conidiophores) and hyphae of the fungus Aspergillus fumigatus. (Image by Kateryna Kon/Science Photo Library via Getty Images)

Computer illustration of fruiting bodies (conidiophores) and hyphae of the fungus Aspergillus fumigatus. (Image by Kateryna Kon/Science Photo Library via Getty Images)

Drug researchers think fungi could once again be a source of life-changing medicines.

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.

For instance, chemical and biomolecular engineer Dr Xue Sherry Gao在新的选项卡/窗口中打开 and a team of researchers at Rice University recently discovered they can use gene editing technology, called multiplex base-editing, to coax fungi to reveal a larger number of natural compounds — and in a much faster timeframe than previously possible. “We created a new machinery that enables base-editing to work on multiple genomic sites, hence the 'multiplex,’” Dr Gao said about the technique在新的选项卡/窗口中打开.

“These compounds could be useful antibiotics or anticancer drugs,” she explained. “We are in the process of figuring out what the biological functions of these compounds are, and we are collaborating with groups in the Baylor College of Medicine on pharmacological small-molecule drug discovery.”

Xue Sherry Gao (Photo by Jeff Fitlow/Rice University)

Xue Sherry Gao (Photo by Jeff Fitlow/Rice University)

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.

Because there is still so much unknown about what fungi have to offer in drug discovery and development, scientists working in this area must have access to a broad range of research. Elsevier solutions have a lot to offer researchers interested in this area. A journal like Fungal Biology在新的选项卡/窗口中打开, available via ScienceDirect, could provide crucial knowledge and insight. Meanwhile Scopus在新的选项卡/窗口中打开 can help researchers identify others specializing in this or related topics for possible collaboration.

The future is fungal

While fungi have always proven to be both friend and foe to humans and our habitats, we can be optimistic that there is much more good to come from our fungal neighbors as pharmaceutical researchers discover more potential lifesaving properties within these fascinating organisms.

Cover of the journal Fungal Biology, published by Elsevier on behalf of The British Mycological Society.

Fungal Biology在新的选项卡/窗口中打开 is published by Elsevier on behalf of the British Mycological Society.

撰稿人

Ann-Marie Roche

AR

Ann-Marie Roche

Senior Director of Customer Engagement Marketing

Elsevier

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