美研究发现：胞苷和健泽合用可杀艾滋病病毒

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胞苷和健泽合用可杀艾滋病病毒  

　　本报华盛顿8月20日电 （记者毛黎）美国明尼苏达大学医疗中心科学家日前表示，他们发现美国食品和药物管理局批准的、目前用于癌症早期和癌症治疗的两种药物胞苷（decitabine）和健泽（gemcitabine）配合使用，有望有效地治疗艾滋病。在实验鼠动物模式研究中，混合药物能够导致艾滋病病毒发生变异并死亡，科学家称其为“致命性变异”。   

　　新发现对艾滋病研究具有划时代的意义，因为这是人们首次寻找到无毒性副作用对付艾滋病病毒的方法。科学家相信，由于胞苷和健泽是两种获准使用的药物，因而如果他们的研究结果在大的实验动物模型上也行之有效的话，那么将比较容易地加速开发出适合于人体的药物。   

　　研究参与人员包括分子病毒研究所和牙科学院的分子病毒学家路易斯·曼斯基博士和克莉丝汀·克劳瑟博士，以及药物设计中心药物化学家史蒂文·帕特森博士。曼斯基表示，他们的发现为最终帮助全球3300万艾滋病病毒携带者解除病症带来了希望。相关文章发表在近期的《病毒学》杂志网站上。   

　　艾滋病病毒在人体内变异和演变迅速。现在常用的药物主要作用是抑制病毒的生长和复制，胞苷和健泽组成的新药物的作用则正好相反，它迫使病毒发生变异失控，并走向灭亡。曼斯基说，艾滋病病毒的变异能力使得人们难以捕捉并对付它，“我们利用了病毒的这一行为，通过促进病毒变异率，让病毒本身作为武器攻击自己”。   

　　科学家发现，他们用来杀灭艾滋病病毒所需药物的浓度对细胞无可检测出的毒性，与此同时，用于有效杀灭实验室培养的艾滋病病毒的药物浓度远低于人们用这两种药治疗癌症时的药物浓度。现有获准使用药物被用来开发治疗其他疾病的方法，在医学界被认为是一种低成本和快速获取新药的途径，称为药物重新定位（drug repositioning）。

　　据悉，胞苷和健泽已获准进行实验鼠的前期临床实验，初期的发现确认，药物可作为艾滋病病毒有效的抗病毒治疗方法。目前科学家正在调整药物，以便组成能够被人体吸收的抗艾滋病病毒口服药。



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deng245

哎、又是研究发现的

齐欢畅2

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现在常用的药物主要作用是抑制病毒的生长和复制，胞苷和健泽组成的新药物的作用则正好相反，它迫使病毒发生变异失控，并走向灭亡。

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Journal of Virology, September 2010, p. 9301-9309, Vol. 84, No. 18
0022-538X/10/$012.00+0     doi:10.1128/JVI.01006-10
Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Exploiting Drug Repositioning for Discovery of a Novel HIV Combination Therapy
Christine L. Clouser,1,2 Steven E. Patterson,3 and Louis M. Mansky1,2,3,4*
Institute for Molecular Virology,1 Department of Diagnostic and Biological Sciences, School of Dentistry,2 Center for Drug Design,3 Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota 554554

Received 8 May 2010/ Accepted 29 June 2010

The development of HIV drugs is an expensive and a lengthy process. In this study, we used drug repositioning, a process whereby a drug approved to treat one condition is used to treat a different condition, to identify clinically approved drugs that have anti-HIV activity. The data presented here show that a combination of two clinically approved drugs, decitabine and gemcitabine, reduced HIV infectivity by 73% at concentrations that had minimal antiviral activity when used individually. Decreased infectivity coincided with a significant increase in mutation frequency and a shift in the HIV mutation spectrum. These results indicate that an increased mutational load is the primary antiviral mechanism for inhibiting the generation of infectious progeny virus from provirus. Similar results were seen when decitabine was used in combination with another ribonucleotide reductase inhibitor. Our results suggest that HIV infectivity can be decreased by combining a nucleoside analog that forms noncanonical base pairs with certain ribonucleotide reductase inhibitors. Such drug combinations are relevant since members of these drug classes are used clinically. Our observations support a model in which increased mutation frequency decreases infectivity through lethal mutagenesis.



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* Corresponding author. Mailing address: Institute for Molecular Virology, University of Minnesota, 18-242 Moos Tower, 515 Delaware St. S.E., Minneapolis, MN 55455. Phone: (612) 626-5525. Fax: (612) 626-5515. E-mail: [email protected]

Published ahead of print on 7 July 2010.



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JVI: 两种用于癌症治疗的药物可抑制HIV2010年08月21日 星期六 04:34Researchers at the University of Minnesota Academic Health Center have identified two drugs that, when combined, may serve as an effective treatment for HIV.


The two drugs, decitabine and gemcitabine -- both FDA approved and currently used in pre-cancer and cancer therapy -- were found to eliminate HIV infection in the mouse model by causing the virus to mutate itself to death -- an outcome researchers dubbed "lethal mutagenesis."

This is a landmark finding in HIV research because it is the first time this novel approach has been used to attack the deadly virus without causing toxic side effects. Because decitabine and gemcitabine are already FDA approved, researchers believe that if their research is effective in large animal models, it will be much easier to expedite the development of the drugs for human use.

The study is a collaboration between molecular virologists Louis Mansky, Ph.D., and Christine Clouser, Ph.D., of the Institute for Molecular Virology and School of Dentistry, as well as medicinal chemist Steven Patterson, Ph.D., from the Center for Drug Design. The findings were recently published online in the Journal of Virology.

"The findings provide hope that such an approach will someday help the 33 million people worldwide who currently live with HIV," Mansky said.

Lethal mutagenesis

HIV mutates and evolves quickly. Rather than inhibiting virus growth and replication like current HIV drugs, this new drug combination forces the virus to do just the opposite -- evolve beyond control, to the point of extinction.

"HIV's ability to mutate makes it difficult to target and treat," Mansky said. "We wanted to take advantage of this behavior by stimulating HIV's mutation rate, essentially using the virus as a weapon against itself."

Drug repositioning

One way to decrease cost and expedite the development of novel drugs is by the use of drug repositioning, the process of taking a drug that is used to treat one medical condition, and using it to treat a different illness.

By examining drugs that are already approved by the Food and Drug Administration, the researchers hope to expedite the development of this drug combination because the safety profiles of the two drugs are known.

U of M researchers found that the drug concentrations needed to eliminate HIV infection cause no measureable cell toxicity and were effective against HIV cultures at concentrations well below the current levels used for cancer treatment.

The path ahead

Gemcitabine and decitabine have been administered in pre-clinical trials with mice. Initial findings confirm that the drugs are an effective antiviral therapy for HIV.

The researchers are now in the process of modifying the drugs to forms that can be absorbed by the human body when taken orally.

来源： http://jvi.asm.org/cgi/content/abstract/84/18/9301

疯一点好

好消息，攻克艾滋病就有可能攻克乙肝，感谢艾滋病人为我们做出的贡献，同时也希望他们可以从此获得彻底根治，那我们也就可以同样受益。不过“致命性变异”的字眼有点吓人，别导致突变就好。

齐欢畅2

这个办法还是前段时间的基因治疗法好，这个风险不小~~

肝与玫瑰

等待等待啊