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Article: A novel small-molecule inhibitor of the avian influenza H5N1 virus determined through computational screening against the neuraminidase

TitleA novel small-molecule inhibitor of the avian influenza H5N1 virus determined through computational screening against the neuraminidase
Authors
Issue Date2009
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/jmc
Citation
Journal Of Medicinal Chemistry, 2009, v. 52 n. 9, p. 2667-2672 How to Cite?
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. © 2009 American Chemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/59418
ISSN
2013 Impact Factor: 5.480
2013 SCImago Journal Rankings: 2.348
ISI Accession Number ID
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.

References
Grants

 

Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. British Columbia Cancer Agency
DC FieldValueLanguage
dc.contributor.authorAn, Jen_HK
dc.contributor.authorLee, DCWen_HK
dc.contributor.authorLaw, AHYen_HK
dc.contributor.authorYang, CLHen_HK
dc.contributor.authorPoon, LLMen_HK
dc.contributor.authorLau, ASYen_HK
dc.contributor.authorJones, SJMen_HK
dc.date.accessioned2010-05-31T03:49:42Z-
dc.date.available2010-05-31T03:49:42Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Medicinal Chemistry, 2009, v. 52 n. 9, p. 2667-2672en_HK
dc.identifier.issn0022-2623en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59418-
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.en_HK
dc.languageengen_HK
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/jmcen_HK
dc.relation.ispartofJournal of Medicinal Chemistryen_HK
dc.titleA novel small-molecule inhibitor of the avian influenza H5N1 virus determined through computational screening against the neuraminidaseen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-2623&volume=52&issue=9&spage=2667&epage=2672&date=2009&atitle=A+novel+small-molecule+inhibitor+of+the+avian+influenza+H5N1+virus+determined+through+computational+screening+against+the+neuraminidaseen_HK
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hken_HK
dc.identifier.emailLau, ASY: asylau@hku.hken_HK
dc.identifier.authorityPoon, LLM=rp00484en_HK
dc.identifier.authorityLau, ASY=rp00474en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1021/jm800455gen_HK
dc.identifier.pmid19419201en_HK
dc.identifier.scopuseid_2-s2.0-65649103683en_HK
dc.identifier.hkuros159177en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65649103683&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume52en_HK
dc.identifier.issue9en_HK
dc.identifier.spage2667en_HK
dc.identifier.epage2672en_HK
dc.identifier.isiWOS:000265911800004-
dc.publisher.placeUnited Statesen_HK
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dc.identifier.f10001160465-
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridAn, J=35739710500en_HK
dc.identifier.scopusauthoridLee, DCW=15751156000en_HK
dc.identifier.scopusauthoridLaw, AHY=8692488400en_HK
dc.identifier.scopusauthoridYang, CLH=26668171500en_HK
dc.identifier.scopusauthoridPoon, LLM=7005441747en_HK
dc.identifier.scopusauthoridLau, ASY=7202626202en_HK
dc.identifier.scopusauthoridJones, SJM=35379604800en_HK
dc.identifier.citeulike4373289-

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