tetano
Editor, Senior Moderator
J Med Chem
. 2024 Feb 1.
doi: 10.1021/acs.jmedchem.3c01715. Online ahead of print. Discovery of a Macrocyclic Influenza Cap-Dependent Endonuclease Inhibitor
Jiajie Feng[SUP] 1 [/SUP], Fengying Guo[SUP] 1 [/SUP], Peng Li[SUP] 1 [/SUP], Jing Zhang[SUP] 2 [/SUP], Kaixuan Jiang[SUP] 1 [/SUP], Zhenzhen Zhu[SUP] 1 [/SUP], Shanshan Yin[SUP] 1 [/SUP], Xiaowan Lin[SUP] 1 [/SUP], Fusen Lin[SUP] 1 [/SUP], Fubiao Xiao[SUP] 1 [/SUP], Xiaoxia Xue[SUP] 2 [/SUP], Haiying He[SUP] 1 [/SUP], Shuhui Chen[SUP] 1 [/SUP]
Affiliations
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.
. 2024 Feb 1.
doi: 10.1021/acs.jmedchem.3c01715. Online ahead of print. Discovery of a Macrocyclic Influenza Cap-Dependent Endonuclease Inhibitor
Jiajie Feng[SUP] 1 [/SUP], Fengying Guo[SUP] 1 [/SUP], Peng Li[SUP] 1 [/SUP], Jing Zhang[SUP] 2 [/SUP], Kaixuan Jiang[SUP] 1 [/SUP], Zhenzhen Zhu[SUP] 1 [/SUP], Shanshan Yin[SUP] 1 [/SUP], Xiaowan Lin[SUP] 1 [/SUP], Fusen Lin[SUP] 1 [/SUP], Fubiao Xiao[SUP] 1 [/SUP], Xiaoxia Xue[SUP] 2 [/SUP], Haiying He[SUP] 1 [/SUP], Shuhui Chen[SUP] 1 [/SUP]
Affiliations
- PMID: 38301207
- DOI: 10.1021/acs.jmedchem.3c01715
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.