ArticleProceedings of the National Academy of Sciences of the United States of America2026
Targeting the polyene chain represents an adjuvant strategy for optimizing polyene antifungals.
Yishan Zhang, Xiaocong Liu, Luobei Weng, Shuixiu Li, Peiran Chen, Gehua Zhang, Jianqi Wang, Dongmei Zhang, Chuanyan Tang, Yunfeng Hu and 2 more
Abstract read
In one paragraphArticle in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
12 authors.
Yishan Zhang *State Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.
Xiaocong Liu *State Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.
Luobei Weng *State Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.
Shuixiu LiState Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.
Peiran ChenState Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.
Gehua ZhangDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou, Guangdong 510630, China.
Jianqi WangDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou, Guangdong 510630, China.
Dongmei ZhangState Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.
Chuanyan TangState Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.
Yunfeng HuState Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.
Wencai YeState Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.ORCID 0000-0002-2810-1001 Hong ZhangState Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.ORCID 0000-0002-5063-4082 Funding
Guangdong Engineering Technology Research Center of Skin Health and Disease 2023A171Innovation Team Project of Universities in Guangdong Province 2022KCXTD002MOE | Fundamental Research Funds for the Central Universities (Fundamental Research Fund for the Central Universities) 21623117MOST | National Key Research and Development Program of China (NKPs) 2021YFC2300400MOST | National Natural Science Foundation of China (NSFC) 82202545MOST | National Natural Science Foundation of China (NSFC) 82272357/82472306Science and Techonology Projects in Guangzhou 2025A03J3629/2025A04J3718
6 · The paper itselfAbstract
Polyene antifungals (PAs) have long constituted an irreplaceable lifesaving treatment for lethal fungal infections. However, PAs induce significant dose-dependent nephrotoxicity, primarily because of their binding to cholesterol in the renal cell membrane, which is structurally similar to their fungicidal target ergosterol in the fungal membrane. Efforts to optimize PAs have focused mainly on their mycosamine group and polyol chain, while the potential of the polyene chain remains underexplored. Here, we report that the polyene chain can function as a molecular switch, enabling hydrophobic coupling with structurally compatible adjuvants repurposed from clinically approved drugs. This hydrophobic coupling triggers conformational rearrangements of PAs, which are characterized by a reorientation of the mycosamine group, and increases the rigidity and length of the polyene chain, which can asymmetrically modulate the binding of PAs to membrane cholesterol and ergosterol, thereby attenuating nephrotoxicity and increasing effectiveness. Among them, vitamin D
Indexed as
Antifungal AgentsPolyenesAnimalsCholesterolErgosterolHumansHydrophobic and Hydrophilic InteractionsAntifungal AgentsCholesterolErgosterolPolyenesamphotericin Bdrug optimizationinvasive fungal infectionpolyene antifungalsvitamin D
Identifiers
PMID42012944
PMCPMC13123897
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LicenceCC BY-NC-ND
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