治疗隐球菌感染新药研究进展

Novel antifungal agents against cryptococcal infections

隐球菌感染每年导致超100万例患者新增感染及近60万例病死报道,严重威胁公众健康。隐球菌对目前有限的抗菌药物的耐药性日益严重,新药研究十分迫切。抗隐球菌药物发挥药效除需具备一般抗真菌药物的特点外,还需进入宿主细胞以及穿透血脑屏障。筛选具有全新作用机制的小分子化合物和已上市药物"老药新用"是目前抗隐球菌药物研发的两种主要策略。本文综述了据此获得的抗隐球菌先导化合物或药物的抗菌活性、作用机制和临床研究进展。

Cryptococcal meningitis, caused by fungus Cryptococcus neoformans, is responsible for over a million infections and 600 000 deaths annually. Largely due to the limited treatment options and the intrinsic drawbacks coupled with drug resistance to current therapies, it is urgent to discover novel antifungal agents against cryptococcosis. An ideal antifungal drug should at least satisfy the following criteria： fungicidal, fungus-specific, permeable for the host barriers such as cell membranes of phagocytes and the blood-CNS barrier Both discovery of candidates with novel mode of action and repurposing existing molecules with potent anti- cryptococcal activity are effective ways in discovery of new anti-cryptococcal agents. Here, we summarized recent advances in the study of anti-fungal activities, mechanisms of action, and clinical developments of new anti-cryptococcal drugs.