Antifungal Drugs: Can New Targets Overcome Resistance?

Why does the antifungal drug pipeline need more options?

The Nature editorial behind the headline was published on April 15, 2025. It called for stronger investment in antifungal discovery and coordinated clinical trials. A central obstacle is biological: fungal cells share more features with human cells than bacteria do, making it difficult to identify drug targets that can be attacked without harming patients. [Nature editorial](https://www.nature.com/articles/d41586-025-01177-x)

WHO's review provides a dated baseline for that concern. As of September 30, 2024, it counted 21 agents in clinical development: nine novel candidates, eight proposed extensions of existing indications and four repurposed medicines. Three of the nine novel candidates were in phase 3. These categories matter because testing an established medicine for another infection does not necessarily introduce a different mechanism for overcoming resistance. The figures describe that historical snapshot rather than an October 2026 pipeline update. [WHO pipeline dashboard](https://www.who.int/observatories/global-observatory-on-health-research-and-development/monitoring/antifungal-agents-in-development)

How could mandimycin offer a different antifungal approach?

In research published in Nature on March 19, 2025, Qisen Deng and colleagues described mandimycin, a compound produced by bacteria. Established polyene antifungals such as amphotericin B target ergosterol, a component of fungal membranes. Mandimycin instead bound several phospholipids, another group of membrane components, disrupting membrane function and allowing essential ions to escape. The investigators reported activity against multiple drug-resistant fungi in laboratory experiments and efficacy in animal infection models. [Mandimycin research](https://www.nature.com/articles/s41586-025-08678-9)

The study also reported encouraging experimental toxicity findings, including comparisons with amphotericin B. However, these were preclinical results. They do not establish a safe human dose, clinical effectiveness or superiority over established treatment. A different molecular target may help bypass some existing resistance mechanisms, but it cannot guarantee that resistance will never emerge. The clinical question is whether this approach can ultimately improve outcomes at exposures patients can tolerate.

What must new antifungal treatments demonstrate in patients?

WHO identified major shortcomings in existing antifungal treatment, including adverse effects, drug interactions and limited dosage forms. These problems are especially relevant to people receiving chemotherapy, transplant recipients and others with weakened immune systems. WHO also highlighted limited pediatric trials and age-appropriate formulations. [WHO treatment and diagnostic assessment](https://www.who.int/news/item/01-04-2025-who-issues-its-first-ever-reports-on-tests-and-treatments-for-fungal-infections)

Clinical development is complicated because serious fungal infections often occur alongside other illnesses. Nature proposed coordinated trial networks to help recruit patients and standardize study methods. Better diagnostic access is also essential: identifying the infection and whether resistance is present helps clinicians select an appropriate treatment. Together, these needs show why discovering an active molecule is only one part of delivering a useful medicine. [Nature editorial](https://www.nature.com/articles/d41586-025-01177-x)