A Novel Small-Molecule Inhibitor of the Avian Influenza H5N1 Virus Determined through Computational Screening against the Neuraminidase

Citations Over TimeTop 10% of 2009 papers

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 Papers

• → Comparison of the Anti-Influenza Virus Activity of RWJ-270201 with Those of Oseltamivir and Zanamivir(2001)148 cited
• → A Novel Small-Molecule Inhibitor of the Avian Influenza H5N1 Virus Determined through Computational Screening against the Neuraminidase(2009)63 cited
• → Frequency of Drug-resistant Viruses and Virus Shedding in Pediatric Influenza Patients Treated With Neuraminidase Inhibitors(2011)50 cited
• → Resistance profiles for the investigational neuraminidase inhibitor AV5080 in influenza A and B viruses(2023)5 cited
• → Surveillance for neuraminidase inhibitor resistance in human influenza viruses from Australia(2003)12 cited