A novel small-molecule inhibitor of the avian influenza H5N1 virus determined through computational screening against the neuraminidase.
Jianghong An, Davy C W Lee, Anna H Y Law, Cindy L H Yang, Leo L M Poon, Allan S Y Lau, Steven J M Jones
Index: J. Med. Chem. 52 , 2667-72, (2009)
Full Text: HTML
Abstract
Computational molecular docking provides an efficient and innovative approach to examine small molecule and protein interactions. We have utilized this method to identify potential inhibitors of the H5N1 neuraminidase protein. Of the 20 compounds tested, 4-(4-((3-(2-amino-4-hydroxy-6-methyl-5-pyrimidinyl)propyl)amino)phenyl)-1-chloro-3-buten-2-one (1) (NSC89853) demonstrated the ability to inhibit viral replication at a level comparable to the known neuraminidase inhibitor oseltamivir. Compound 1 demonstrated efficacy across a number of cell-lines assays and in both the H1N1 and H5N1 viruses. The predicted binding of 1 to the known H5N1 neuraminidase structure indicates a binding interface largely nonoverlapping with that of oseltamivir or another neuraminidase inhibitor zanamivir. These results indicate that 1 or similar molecules would remain effective in the presence of virus mutations conferring resistance to either oseltamivir or zanamivir and also vice versa.
Related Compounds
Related Articles:
Enantioselective nanofiber-spinning of chiral calixarene receptor with guest.
2007-08-28
[Chem. Commun. (Camb.) (32) , 3398-400, (2007)]
New alpha-amino phosphonic acid derivatives of vinblastine: chemistry and antitumor activity.
1991-07-01
[J. Med. Chem. 34 , 1998, (1991)]
2004-04-15
[Org. Lett. 6(8) , 1189-92, (2004)]
2004-04-01
[J. Pharmacol. Exp. Ther. 309(1) , 173-81, (2004)]
Heat-set gels and egg-like vesicles using two component gel system based on chiral calix[4]arenes.
2007-12-28
[Chem. Commun. (Camb.) (48) , 5200-2, (2007)]