Accelerated Discovery of Potent Fusion Inhibitors for Respiratory Syncytial Virus.
Accelerated Discovery of Potent Fusion Inhibitors for Respiratory Syncytial Virus.
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加速发现呼吸道合胞病毒的强效融合抑制剂。
DOI：
10.1021/acsinfecdis.9b00524
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发表时间：
2020
影响因子：
5.3
通讯作者：
Liotta,D
中科院分区：
文献类型：
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作者：
Pribut,Nicole;Kaiser,ThomasM;Wilson,RobertJ;Jecs,Edgars;Dentmon,ZackeryW;Pelly,StephenC;Sharma,Savita;Bartsch3rd,PerryW;Burger,PieterB;Hwang,SoyonS;Le,Thalia;Sourimant,Julien;Yoon,Jeong-Joong;Plemper,RichardK;Liotta,D
使用机器学习算法鉴定了一系列五种基于苯并咪唑的化合物作为呼吸道合胞病毒（RSV）融合蛋白的潜在抑制剂。合成了这些化合物，其中化合物2表现出优异的体外活性，其EC 50值为5 nM。然后对这种新支架进行进一步改进，从而鉴定出化合物44，其活性提高了10倍，EC50值为0.5 nM。
A series of five benzimidazole-based compounds were identified using a machine learning algorithm as potential inhibitors of the respiratory syncytial virus (RSV) fusion protein. These compounds were synthesized, and compound2in particular exhibited excellentin vitropotency with an EC50value of 5 nM. This new scaffold was then further refined leading to the identification of compound44, which exhibited a 10-fold improvement in activity with an EC50value of 0.5 nM.