[1]石会娜,栗海波,刘伟#.H1N1流感病毒D151G突变株对奥司他韦的抗药性研究及药物筛选[J].郑州大学学报(医学版),2011,(05):711-68.
 SHI Huina,LI Haibo,LIU Wei.Drug resistance of mutation D151G of H1N1 influenza virus to oseltamivir and drug screening[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2011,(05):711-68.
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H1N1流感病毒D151G突变株对奥司他韦的抗药性研究及药物筛选
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2011年05期
页码:
711-68
栏目:
论著
出版日期:
2011-09-20

文章信息/Info

Title:
Drug resistance of mutation D151G of H1N1 influenza virus to oseltamivir and drug screening
作者:
石会娜栗海波刘伟#
郑州大学生物工程系 郑州 450001
Author(s):
SHI Huina LI Haibo LIU Wei
Department of Bioengineering, Zhengzhou University, Zhengzhou 450001
关键词:
H1N1流感病毒奥司他韦神经氨酸酶分子对接药物筛选
Keywords:
H1N1 influenza virusoseltamivirneuraminidase molecular docking drug screening
分类号:
R511.7
摘要:
目的:观察H1N1流感病毒D151G突变株对奥司他韦的抗药性,筛选对D151G突变神经氨酸酶具有抑制作用的化合物。方法:采用分子动力学模拟和MMGBSA自由能计算方法判断H1N1流感病毒D151G突变株对奥司他韦的抗药性;应用分子对接软件Autodock从ZINC数据库筛选与D151G突变神经氨酸酶结合能力较强的化合物。结果:D151G突变神经氨酸酶与奥司他韦的结合能比野生型神经氨酸酶与奥司他韦的结合能降低了-4.61 kcal/mol;筛选出的5个化合物及奥司他韦与D151G突变神经氨酸酶的结合能分别为-7.56、-7.71、-7.88、-7.89、-9.09和-7.21 kcal/mol。结论:H1N1流感病毒D151G突变株对奥司他韦具有抗药性,筛选出的5个化合物中,4[1(1金刚烷基氧化羧基)乙氨基]3氨基4氧代丁酸与D151G突变神经氨酸酶的结合能力最强。
Abstract:
Aim:To observe whether mutation D151G of H1N1 influenza virus exhibits drug resistance to oseltamivir and select compounds to which mutation D151G of H1N1 influenza virus is sensitive.Methods:Molecular dynamics simulation and MMGBSA methods were performed to judge the resistance of mutation D151G of H1N1 influenza virus to oseltamivir; molecular docking software Autodock was applied to select some compounds from ZINC database, which had higher affinity to D151G mutated neuraminidase than oseltamivir.Results:The binding energy of D151G mutated neuraminidase to oseltamivir decreased by -4.61 kcal/mol with respect to wildtype complex. The binding energies of five compounds and oseltamivir to D151G mutated neuraminidase were -7.56,-7.71,-7.88,-7.89,-9.09 and -7.21 kcal/mol,respectively.Conclusion: Mutation D151G of H1N1 influenza virus exhibits drug resistance to oseltamivir. 4[1(1adamantyloxycarbonyl)ethylamino]3amino4oxobutanoic acid has highest affinity to D151G mutated neuraminidase among five candidate compounds.

参考文献/References:

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备注/Memo

备注/Memo:
#通讯作者,男,1967年7月生,博士,教授,研究方向:生物信息学与药物设计,Email: weiliu@zzu.edu.cn
更新日期/Last Update: 2011-09-20