化学
核酸内切酶
立体化学
酶抑制剂
结构-活动关系
生物化学
酶
体外
作者
Junbo Feng,Fengying Guo,P. Andy Li,Jing Zhang,Kaixuan Jiang,Zhen Zhu,Shanshan Yin,Xiaowan Lin,Fusen Lin,Fubiao Xiao,Xiaoxia Xue,Haiying He,Shuhui Chen
标识
DOI:10.1021/acs.jmedchem.3c01715
摘要
Influenza viruses (IFVs) have caused several pandemics and have claimed numerous lives since their first record in the early 20th century. While the outbreak of COVID-19 seemed to expel influenza from the sight of people for a short period of time, it is not surprising that it will recirculate around the globe after the coronavirus has mutated into a less fatal variant. Baloxavir marboxil (1), the prodrug of baloxavir (2) and a cap-dependent endonuclease (CEN) inhibitor, were approved by the FDA for the first treatment in almost 20 years. Despite their high antiviral potency, drug-resistant variants have been observed in clinical trials. Herein, we report a novel CEN inhibitor 8 with a delicately designed macrocyclic scaffold that exhibits a significantly smaller shift of inhibitory activity toward baloxavir-resistant variants.
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