| Description |
Based on the epidemiological and propagation patterns, pathogenic resistance and host interaction mechanisms of important pathogenic fungi, develop two sets of fast and convenient universal fungal infection diagnosis and identification methods, including precise molecular diagnosis and rapid in vitro culture techniques; screen lead compounds targeting cell wall synthesis and mitochondrial metabolism to develop novel antifungal drugs; and based on the host interaction mechanisms, develop antibody therapeutic technologies for important pathogenic fungi. Based on group screening or key regulatory genes of cell wall synthesis and key factors of mitochondrial metabolism, analyze the structure of related proteins, and synthesize antifungal compounds with high activity, such as lead compounds targeting Candida mitochondria-specific protein Mcu1. In addition, the long-term widespread clinical use of azole antifungal drugs targeting the fungus Cyp51 (Erg11) has led to a growing problem of drug resistance. Using the mechanism of interaction between fungal Cyp51 and Ncp1 protein in catalyzing the oxidative demethylation reaction of lanosterol, we proposed to select new antifungal lead compounds targeting this interaction as well as different sites of Cyp51 to obtain new antifungal lead compounds with strong antifungal activity, but also acting on the new and different active sites of Cyp51, avoiding the cross-resistance. |
