Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine
The 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 com...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/1721.1/69046 |
| _version_ | 1811095194433486848 |
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| author | Chen, Yu-Chian Chang, Su-Sen Huang, Hung-Jin |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Chen, Yu-Chian Chang, Su-Sen Huang, Hung-Jin |
| author_sort | Chen, Yu-Chian |
| collection | MIT |
| description | The 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. |
| first_indexed | 2024-09-23T16:12:14Z |
| format | Article |
| id | mit-1721.1/69046 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:12:14Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/690462022-09-29T18:55:35Z Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine Chen, Yu-Chian Chang, Su-Sen Huang, Hung-Jin Massachusetts Institute of Technology. Computational and Systems Biology Program Chen, Yu-Chian Chen, Yu-Chian The 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. National Science Council of Taiwan (NSC 99-2221-E-039-013-) Committee on Chinese Medicine and Pharmacy (CCMP100-RD-030) China Medical University and Asia University (CMU98-TCM) China Medical University and Asia University (CMU99-TCM) China Medical University and Asia University (CMU99-S-02) China Medical University and Asia University (CMU99-ASIA-25) China Medical University and Asia University (CMU99-ASIA-26) China Medical University and Asia University (CMU99-ASIA-27) China Medical University and Asia University (CMU99-ASIA-28) Taiwan Department of Health. Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004) Taiwan Department of Health. Cancer Research Center of Excellence (DOH100-TD-C-111-005) 2012-02-08T18:56:34Z 2012-02-08T18:56:34Z 2011-12 2011-07 Article http://purl.org/eprint/type/JournalArticle 1553-734X 1553-7358 http://hdl.handle.net/1721.1/69046 Chang, 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 http://dx.doi.org/10.1371/journal.pcbi.1002315 PLoS Computational Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Chen, Yu-Chian Chang, Su-Sen Huang, Hung-Jin Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine |
| title | Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine |
| title_full | Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine |
| title_fullStr | Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine |
| title_full_unstemmed | Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine |
| title_short | Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine |
| title_sort | two birds with one stone possible dual targeting h1n1 inhibitors from traditional chinese medicine |
| url | http://hdl.handle.net/1721.1/69046 |
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