Identification of hits as matrix-2 protein inhibitors through the focused screening of a small primary amine library.
Although amantadine derivatives are the only M2 drugs for influenza virus A, their use is limited in the U.S. because of drug resistance. Here we report the identification of multiple M2 inhibitors that were rapidly generated through focused screening of a small primary amine library that was designed using a scaffold-hopping strategy based on amantadine. These compounds are as active as amantadine and might be hits for further lead generation processes.
Hu
Wenhui
W
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Science Park, Guangdong 510530, People's Republic of China. hu_wenhui@gibh.ac.cn
Zeng
Shaogao
S
Li
Chufang
C
Jie
Yanling
Y
Li
Zhiyuan
Z
Chen
Ling
L
D000547:Amantadine / Q000494:pharmacology; D000588:Amines / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D024882:Drug Resistance, Viral; D009980:Influenza A virus / Q000187:drug effects*; D054852:Small Molecule Libraries; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors*; D000086082:Viroporin Proteins
D000547:Amantadine; D000588:Amines; D000998:Antiviral Agents; D054852:Small Molecule Libraries; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins