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Article: A novel small-molecule inhibitor of the avian influenza H5N1 virus determined through computational screening against the neuraminidase
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TitleA novel small-molecule inhibitor of the avian influenza H5N1 virus determined through computational screening against the neuraminidase
 
AuthorsAn, J2
Lee, DCW1
Law, AHY1
Yang, CLH1
Poon, LLM1
Lau, ASY1
Jones, SJM2
 
Issue Date2009
 
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/jmc
 
CitationJournal Of Medicinal Chemistry, 2009, v. 52 n. 9, p. 2667-2672 [How to Cite?]
DOI: http://dx.doi.org/10.1021/jm800455g
 
AbstractComputational 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. © 2009 American Chemical Society.
 
ISSN0022-2623
2013 Impact Factor: 5.480
2013 SCImago Journal Rankings: 2.348
 
DOIhttp://dx.doi.org/10.1021/jm800455g
 
ISI Accession Number IDWOS:000265911800004
Funding AgencyGrant Number
Michael Smith Foundation for Health Research
Area of Excellence Scheme of the University Grants CommitteeAoE/M-12/06
Funding Information:

We are grateful to the Developmental Therapeutics Program, National Cancer Institute, USA, for providing the chemical compounds in this project. S.J.M.J. is a scholar of the Michael Smith Foundation for Health Research. The project is funded in part by the Area of Excellence Scheme of the University Grants Committee (Grant AoE/M-12/06) of Hong Kong and Prof. Francis SK Lau Research Fund awarded to Dr. A. Lau.

 
ReferencesReferences in Scopus
 
GrantsControl of Pandemic and Inter-pandemic Influenza
 
DC FieldValue
dc.contributor.authorAn, J
 
dc.contributor.authorLee, DCW
 
dc.contributor.authorLaw, AHY
 
dc.contributor.authorYang, CLH
 
dc.contributor.authorPoon, LLM
 
dc.contributor.authorLau, ASY
 
dc.contributor.authorJones, SJM
 
dc.date.accessioned2010-05-31T03:49:42Z
 
dc.date.available2010-05-31T03:49:42Z
 
dc.date.issued2009
 
dc.description.abstractComputational 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. © 2009 American Chemical Society.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Medicinal Chemistry, 2009, v. 52 n. 9, p. 2667-2672 [How to Cite?]
DOI: http://dx.doi.org/10.1021/jm800455g
 
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Funding AgencyGrant Number
Michael Smith Foundation for Health Research
Area of Excellence Scheme of the University Grants CommitteeAoE/M-12/06
Funding Information:

We are grateful to the Developmental Therapeutics Program, National Cancer Institute, USA, for providing the chemical compounds in this project. S.J.M.J. is a scholar of the Michael Smith Foundation for Health Research. The project is funded in part by the Area of Excellence Scheme of the University Grants Committee (Grant AoE/M-12/06) of Hong Kong and Prof. Francis SK Lau Research Fund awarded to Dr. A. Lau.

 
dc.identifier.issn0022-2623
2013 Impact Factor: 5.480
2013 SCImago Journal Rankings: 2.348
 
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dc.languageeng
 
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/jmc
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Medicinal Chemistry
 
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza
 
dc.relation.referencesReferences in Scopus
 
dc.titleA novel small-molecule inhibitor of the avian influenza H5N1 virus determined through computational screening against the neuraminidase
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. British Columbia Cancer Agency