Antifungal drug discovery: the process and outcomes.
Antifungal drug discovery: the process and outcomes.
复制标题
DOI：
10.2217/fmb.14.32
复制
发表时间：
2014
影响因子：
3.1
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
Calderone R;Sun N;Gay-Andrieu F;Groutas W;Weerawarna P;Prasad S;Alex D;Li D
新的数据表明，几种真菌疾病的全球发病率传统上文献记载不足。其中，侵袭性真菌感染造成的死亡率仍然高得令人不安，等于或超过耐药结核病和疟疾造成的死亡率。显然，需要对新的抗真菌药物、疫苗和诊断工具进行基础研究。本文综述了抗真菌药物的发现，包括体外检测、化合物文库和靶点鉴定方法。基因组挖掘使鉴定真菌特异性靶点成为可能；然而，针对这些目标的新化合物显然不在抗菌管道中。我们建议“重新利用”化合物（非专利）可能是一个更直接的起点。此外，我们研究了抗真菌发现的教条，并建议在结构生物学、同源建模和虚拟成像等技术方面进行重大推动，以推动发现。
New data suggest that the global incidence of several types of fungal diseases have traditionally been under-documented. Of these, mortality caused by invasive fungal infections remains disturbingly high, equal to or exceeding deaths caused by drug-resistant tuberculosis and malaria. It is clear that basic research on new antifungal drugs, vaccines and diagnostic tools is needed. In this review, we focus upon antifungal drug discovery including in vitro assays, compound libraries and approaches to target identification. Genome mining has made it possible to identify fungal-specific targets; however, new compounds to these targets are apparently not in the antimicrobial pipeline. We suggest that ‘repurposing’ compounds (off patent) might be a more immediate starting point. Furthermore, we examine the dogma on antifungal discovery and suggest that a major thrust in technologies such as structural biology, homology modeling and virtual imaging is needed to drive discovery.