Structure-based tetravalent zanamivir with potent inhibitory activity against drug-resistant influenza viruses
文献类型：期刊论文
| 作者 | Fu, Lifeng1,2,3; Bi, Yuhai1; Wu, Yan1; Zhang, Shanshan1,3; Qi, Jianxun1; Li, Yan1; Lu, Xuancheng4; Zhang, Zhenning1,3; Lv, Xun1; Yan, Jinghua1,5 |
| 刊名 | Journal of medicinal chemistry
 |
| 出版日期 | 2016-07-14 |
| 卷号 | 59期号:13页码:6303-6312 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.6b00537 |
| 通讯作者 | Gao, george f.(gaof@im.ac.cn) ; Li, xuebing(lixb@im.ac.cn) |
| 英文摘要 | Zanamivir and oseltamivir are principal influenza antiviral drugs that target viral neuraminidase (na), but resistant viruses containing mutant nas with diminished drug affinity are increasingly emerging. using the structural knowledge of both drug binding sites and their spatial arrangement on the homotetrameric na, we have developed a tetravalent zanamivir (tz) molecule that exhibited marked increases in na binding affinity, inhibition of na enzyme activity, and in vitro plus in vivo antiviral efficacy over zanamivir. tz functioned against both human seasonal h3n2 and avian h7n9 viruses, including drug-resistant mutants. crystal structure of a resistant n9 na in complex with tz explained the function, which showed that four zanamivir residues simultaneously bound to all four monomers of na. the design method of tz described in this study may be useful to develop drugs or ligands that target proteins with multiple binding sites. the potent anti-influenza activity of tz makes it attractive for further development. |
| WOS关键词 | A H7N9 VIRUS ; NEURAMINIDASE INHIBITORS ; SIALIC-ACID ; AVIAN INFLUENZA ; ANTIINFLUENZA ACTIVITY ; PHOSPHONATE CONGENERS ; MAXIMUM-LIKELIHOOD ; H1N1 NEURAMINIDASE ; RECEPTOR-BINDING ; HIGHLY POTENT |
| WOS研究方向 | Pharmacology & Pharmacy |
| WOS类目 | Chemistry, Medicinal |
| 语种 | 英语 |
| WOS记录号 | WOS:000379989800024 |
| 出版者 | AMER CHEMICAL SOC |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2374552 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Gao, George F.; Li, Xuebing |
| 作者单位 | 1.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China 2.Jiangxi Normal Univ, Natl Engn Res Ctr Carbohydrate Synth, Nanchang 330022, Peoples R China 3.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China 4.Chinese Ctr Dis Control & Prevent, Lab Anim Ctr, Beijing 102206, Peoples R China 5.Chinese Acad Sci CASCIRE, Ctr Influenza Res & Early Warning, Beijing 100101, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fu, Lifeng,Bi, Yuhai,Wu, Yan,et al. Structure-based tetravalent zanamivir with potent inhibitory activity against drug-resistant influenza viruses[J]. Journal of medicinal chemistry,2016,59(13):6303-6312. |
| APA | Fu, Lifeng.,Bi, Yuhai.,Wu, Yan.,Zhang, Shanshan.,Qi, Jianxun.,...&Li, Xuebing.(2016).Structure-based tetravalent zanamivir with potent inhibitory activity against drug-resistant influenza viruses.Journal of medicinal chemistry,59(13),6303-6312. |
| MLA | Fu, Lifeng,et al."Structure-based tetravalent zanamivir with potent inhibitory activity against drug-resistant influenza viruses".Journal of medicinal chemistry 59.13(2016):6303-6312. |
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来源：中国科学院大学
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