Sun Cancan, Li Yi, Kidd Justin M, Han Jizhong, Ding Liangliang, May Aaron E, Zhou Lei, Liu Qinglian
Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen 518107, China.
J Fungi (Basel). 2024 Oct 23;10(11):732. doi: 10.3390/jof10110732.
Fungal infections present a significant global health challenge, prompting ongoing research to discover innovative antifungal agents. The 110 kDa heat shock proteins (Hsp110s) are molecular chaperones essential for maintaining cellular protein homeostasis in eukaryotes. Fungal Hsp110s have emerged as a promising target for innovative antifungal strategies. Notably, 2H stands out as a promising candidate in the endeavor to target Hsp110s and combat fungal infections. Our study reveals that 2H exhibits broad-spectrum antifungal activity, effectively disrupting the in vitro chaperone activity of Hsp110 from and inhibiting the growth of . Pharmacokinetic analysis indicates that oral administration of 2H may offer enhanced efficacy compared to intravenous delivery, emphasizing the importance of optimizing the AUC/MIC ratio for advancing its clinical therapy.
真菌感染是一项重大的全球健康挑战,促使人们不断开展研究以发现创新的抗真菌药物。110 kDa热休克蛋白(Hsp110s)是真核生物中维持细胞蛋白质稳态所必需的分子伴侣。真菌Hsp110s已成为创新抗真菌策略的一个有前景的靶点。值得注意的是,在靶向Hsp110s和对抗真菌感染的努力中,2H是一个有前景的候选药物。我们的研究表明,2H具有广谱抗真菌活性,能有效破坏来自[具体来源未提及]的Hsp110的体外伴侣活性,并抑制[具体真菌未提及]的生长。药代动力学分析表明,与静脉给药相比,口服2H可能具有更高的疗效,这强调了优化AUC/MIC比值以推进其临床治疗的重要性。