Candida albicans biofilms are highly resistant to conventional antifungal agents such as fluconazole, largely due to matrix sequestration, efflux pump activation, and altered sterol metabolism. Among its virulence factors, the secreted aspartyl proteinase family (SAPs) plays a pivotal role in tissue invasion, adhesion, and biofilm development. While SAP1-SAP6 have been extensively characterized, SAP5 remains underexplored despite its strong association with biofilm formation and antifungal resistance. This study aimed to evaluate the antifungal potential of bioactive phytometabolites derived from Astilbe rivularis against the biofilm-associated enzyme SAP5 (PDB ID: 2QZX) using computational approaches. Seven major phytometabolites from A. rivularis, retrieved from the IMPPAT database, were analyzed using AutoDock Vina for molecular docking against SAP5. Protein-protein interaction analysis was conducted through the STRING database to assess SAP5’s functional associations. Top-ranked ligands were visualized in PyMol and Discovery Studio to identify key amino acid interactions. Pharmacokinetic and drug-likeness evaluations were performed using SwissADME, while fluconazole served as the reference control. All seven phytometabolites exhibited strong binding affinities toward SAP5, ranging from -6.4 to -8.3 kcal/mol, indicating stable ligand-protein interactions. Key residues involved in binding included Asp218, Thr221, Tyr222, Ser278, Gly287, and Asp290. The STRING network revealed that SAP5 participates in a dense interaction cluster (11 nodes, 48 edges) associated with fungal virulence pathways. ADME profiling confirmed that all compounds satisfied Lipinski’s Rule of Five, displaying high gastrointestinal absorption and favourable drug-likeness comparable to fluconazole. This study provides the first in silico evidence that Astilbe rivularis phytochemicals can act as natural inhibitors of the Candida albicans SAP5 enzyme, potentially disrupting biofilm formation and virulence. The results highlight SAP5 as a promising antifungal target and position A. rivularis as an underexplored plant source for developing resistance-sparing, plant-based therapeutics.
Antifungal phytoconstituents, Aspartyl protease inhibition, Biofilm-associated virulence, Ethnopharmacology, Quorum sensing modulation, Genetics, Disease, Green product
© The Author(s) 2026. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License which permits unrestricted use, sharing, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
