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dc.contributor.authorChen, Yu-Chian
dc.contributor.authorChang, Su-Sen
dc.contributor.authorHuang, Hung-Jin
dc.date.accessioned2012-02-08T18:56:34Z
dc.date.available2012-02-08T18:56:34Z
dc.date.issued2011-12
dc.date.submitted2011-07
dc.identifier.issn1553-734X
dc.identifier.issn1553-7358
dc.identifier.urihttp://hdl.handle.net/1721.1/69046
dc.description.abstractThe H1N1 influenza pandemic of 2009 has claimed over 18,000 lives. During this pandemic, development of drug resistance further complicated efforts to control and treat the widespread illness. This research utilizes traditional Chinese medicine Database@Taiwan (TCM Database@Taiwan) to screen for compounds that simultaneously target H1 and N1 to overcome current difficulties with virus mutations. The top three candidates were de novo derivatives of xylopine and rosmaricine. Bioactivity of the de novo derivatives against N1 were validated by multiple machine learning prediction models. Ability of the de novo compounds to maintain CoMFA/CoMSIA contour and form key interactions implied bioactivity within H1 as well. Addition of a pyridinium fragment was critical to form stable interactions in H1 and N1 as supported by molecular dynamics (MD) simulation. Results from MD, hydrophobic interactions, and torsion angles are consistent and support the findings of docking. Multiple anchors and lack of binding to residues prone to mutation suggest that the TCM de novo derivatives may be resistant to drug resistance and are advantageous over conventional H1N1 treatments such as oseltamivir. These results suggest that the TCM de novo derivatives may be suitable candidates of dual-targeting drugs for influenza.en_US
dc.description.sponsorshipNational Science Council of Taiwan (NSC 99-2221-E-039-013-)en_US
dc.description.sponsorshipCommittee on Chinese Medicine and Pharmacy (CCMP100-RD-030)en_US
dc.description.sponsorshipChina Medical University and Asia University (CMU98-TCM)en_US
dc.description.sponsorshipChina Medical University and Asia University (CMU99-TCM)en_US
dc.description.sponsorshipChina Medical University and Asia University (CMU99-S-02)en_US
dc.description.sponsorshipChina Medical University and Asia University (CMU99-ASIA-25)en_US
dc.description.sponsorshipChina Medical University and Asia University (CMU99-ASIA-26)en_US
dc.description.sponsorshipChina Medical University and Asia University (CMU99-ASIA-27)en_US
dc.description.sponsorshipChina Medical University and Asia University (CMU99-ASIA-28)en_US
dc.description.sponsorshipTaiwan Department of Health. Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004)en_US
dc.description.sponsorshipTaiwan Department of Health. Cancer Research Center of Excellence (DOH100-TD-C-111-005)en_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pcbi.1002315en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en_US
dc.sourcePLoSen_US
dc.titleTwo Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicineen_US
dc.typeArticleen_US
dc.identifier.citationChang, Su-Sen, Hung-Jin Huang, and Calvin Yu-Chian Chen. “Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine.” Ed. Kuo-Chen Chou. PLoS Computational Biology 7.12 (2011): e1002315. Web. 8 Feb. 2012.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Computational and Systems Biology Programen_US
dc.contributor.approverChen, Yu-Chian
dc.contributor.mitauthorChen, Yu-Chian
dc.relation.journalPLoS Computational Biologyen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsChang, Su-Sen; Huang, Hung-Jin; Chen, Calvin Yu-Chianen
mit.licensePUBLISHER_CCen_US


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