Conquering the stronghold: Membrane‐targeting anti‐infective drug discovery
- 1Department of Medicinal Chemistry State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shandong Key Laboratory of Druggability Optimization and Evaluation for Lead Compounds Shandong Basic Science Special Academic Zone (Pharmacy) School of Pharmaceutical Sciences Shandong University Jinan Shandong China
- 2Institute of Poultry Science Shandong Academy of Agricultural Sciences Jinan Shandong China
Abstract
In the realm of anti‐infective drug discovery, traditional paradigms have long been predicated on targeting specific proteins, enzymes, or nucleic acid biosynthetic pathways. However, propelled by the escalating crisis of mutation‐driven resistance, these conventional approaches are currently encountering formidable bottlenecks. Concurrently, despite historical challenges pertaining to selectivity and toxicity, lipid membranes have emerged as validated therapeutic targets in clinical settings. Two seminal studies published in Nature Communications (Buchholz et al. 2025) and Cell (Chen et al. 2026) have highlighted membrane‐associated mechanisms. Respectively, these studies delineate the application of compound XM‐01 as a broad‐spectrum antiviral agent for the development of inactivated vaccines, and demonstrate that the microbial natural product Butyrolactol A (BLA) potentiates antifungal efficacy via the inhibition of the phospholipid flippase complex Apt1–Cdc50. Focusing on the persistent challenges of viral and fungal infections, this perspective article synthesizes the core findings of these two articles. We systematically elucidated the mechanisms of action underlying compound XM‐01 and the natural product BLA, alongside a critical analysis of their physicochemical properties and pharmacokinetic hurdles. Furthermore, we explore the historical context of membrane‐active agents and outline prospective research directions, with the overarching aim of providing valuable insights and inspiration to investigators in this interdisciplinary field.
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BibTeX
@article{hou2026conquering,
title = {{Conquering the stronghold: Membrane‐targeting anti‐infective drug discovery}},
author = {Yanxu Hou and Jiwei Zhang and Bing Huang and Peng Zhan and Xinyong Liu},
journal = {Smart molecules : open access},
year = {2026},
month = oct,
doi = {10.1002/smo2.70116},
url = {https://europepmc.org/article/PMC/PMC13722835},
note = {CC BY},
}
RIS
TY - JOUR
TI - Conquering the stronghold: Membrane‐targeting anti‐infective drug discovery
AU - Yanxu Hou
AU - Jiwei Zhang
AU - Bing Huang
AU - Peng Zhan
AU - Xinyong Liu
PY - 2026
DA - 2026/10/30
JO - Smart molecules : open access
DO - 10.1002/smo2.70116
UR - https://europepmc.org/article/PMC/PMC13722835
AB - In the realm of anti‐infective drug discovery, traditional paradigms have long been predicated on targeting specific proteins, enzymes, or nucleic acid biosynthetic pathways. However, propelled by the escalating crisis of mutation‐driven resistance, these conventional approaches are currently encountering formidable bottlenecks. Concurrently, despite historical challenges pertaining to selectivity and toxicity, lipid membranes have emerged as validated therapeutic targets in clinical settings. Two seminal studies published in Nature Communications (Buchholz et al. 2025) and Cell (Chen et al. 2026) have highlighted membrane‐associated mechanisms. Respectively, these studies delineate the application of compound XM‐01 as a broad‐spectrum antiviral agent for the development of inactivated vaccines, and demonstrate that the microbial natural product Butyrolactol A (BLA) potentiates antifungal efficacy via the inhibition of the phospholipid flippase complex Apt1–Cdc50. Focusing on the persistent challenges of viral and fungal infections, this perspective article synthesizes the core findings of these two articles. We systematically elucidated the mechanisms of action underlying compound XM‐01 and the natural product BLA, alongside a critical analysis of their physicochemical properties and pharmacokinetic hurdles. Furthermore, we explore the historical context of membrane‐active agents and outline prospective research directions, with the overarching aim of providing valuable insights and inspiration to investigators in this interdisciplinary field.
SN - 2751-4595
SN - 2751-4587
ER -