战胜病毒:疱疹病毒攻击新药
John Travis到5约翰
Best known for intermittently producing embarrassing sores on the mouth and genitals, herpes simplex virus (HSV) is more dangerous than most people realize.间歇生产闻名的嘴,尴尬的伤疤性器官疱疹病毒(单纯疱疹病毒)的危险性比一般人明白. The virus can blind and even kill people with weak immune systems, such as newborns, elderly people, and AIDS patients.可以杀死病毒,甚至失明的残疾人弱免疫系统,如新生儿、老人和艾滋病患者.
By targeting one of the virus' enzymes, two pharmaceutical companies have now independently identified a new class of drugs that stop HSV from replicating.针对一个病毒的酶两个制药公司已确定了新的独立阶层,阻止毒品从单纯疱疹病毒. Scientists rate the compounds as the most promising antiherpes agents developed in 3 decades.科学家率作为最有前途的化合物抗剂研制3年. Surprisingly, however, there are no current plans to test the experimental drugs in people.出乎意料,不过,目前没有任何计划测试实验药物在人.
First developed in the 1970s, the compound acyclovir remains the standard drug for treating various forms of HSV.在1970年制订的标准仍阿昔洛韦复方药物治疗各种疱疹. When acyclovir gets into an infected cell, an HSV enzyme activates the drug, leading to the inhibition of a protein the virus uses to copy its own DNA.当阿昔洛韦加入染病细胞,激活酶的疱疹的药物,导致抑制病毒蛋白复制自己的DNA用途. However, a treated infection may recur, and some strains of the virus are resistant to acyclovir.不过,也可能出现感染治疗,有的菌株具有抵抗病毒的阿昔洛韦.
Seeking new drug opportunities, researchers have looked at other proteins that the virus relies on to replicate its DNA.如需新药机遇,研究员看过其他蛋白质,其病毒DNA的复制依赖. More than a decade ago, while at Stanford University, James J. Crute discovered a complex of three HSV proteins that combine into an enzyme called helicase-primase.十多年前,在史丹福大学、詹姆斯Jcrute发现一个复杂的蛋白质结合成三个疱疹解旋酶称为--引. The virus uses this enzyme to unravel DNA's double helix structure and perform other duties required for replication.利用这种酶来破坏病毒的DNA的双螺旋结构和复制所需履行的其他职责.
"It was immediately recognized as a really great target for drug discovery," recalls Crute, now at Aurora Biosciences in San Diego."有人立即确认为真伟大目标药物发现,"回忆crute,目前极光圣迭戈生物科学.
While working at Boehringer Ingelheim Pharmaceutical in Ridgefield, Conn., Crute and his colleagues developed an assay for screening thousands of compounds for ones that inhibit the helicase activity of the viral enzyme.在工作时,在BoehringerIngelheim制药ridgefield,Conn,crute及其同事研制出检测筛选数以千计的化合物,抑制解旋酶活病毒酶. They identified several compounds that hamper the enzyme's ability to creep along the DNA strand and perform its duties.他们发现几个阻碍物酶的能力和蠕变沿着DNA链履行职责.
Crute's team reports in the April Nature Medicine that these inhibitors block HSV replication in infected cells and also help rodents survive HSV infections.crute队在12日的报道自然医学这些抑制剂阻滞疱疹病毒复制细胞和鼠类生存,也有助于疱疹病毒. In mice whose genitals had been infected with HSV, one inhibitor slashed the death rate from 60 percent to 10 percent.在小鼠已感染的生殖器疱疹,其中一刀抑制剂死亡率由60%提高至10%.
Moreover, the new compounds are effective even when given to the mice up to 65 hours after an initial infection.而且,即使是行之有效的新化合物为65个小时之后到小鼠初次感染. In contrast, for acyclovir to work, it must be taken within hours after the first symptoms appear.相比之下,对阿昔洛韦工作,必须在第一时间内采取的症状出现.
Gerald Kleymann and his colleagues at Bayer AG in Wuppertal, Germany, also have identified inhibitors of HSV replication.kleymann杰拉尔德和他的同事在伍珀塔尔拜尔在德国也已确定疱疹复制抑制剂. After screening more than 400,000 compounds, they realized that the most effective ones were interfering with helicase-primase.经过筛选化合物达40多万,他们意识到,最有效的干预是旋-引.
"It appears that we hit the Achilles' heel of the virus," says Kleymann."看来,我们打的软肋病毒",kleymann.
Like the Boehringer Ingelheim team, the Bayer group found the compounds to be effective in rodents infected with HSV.BoehringerIngelheim队一样,拜耳集团的化合物,可有效发现老鼠感染疱疹. In the April Nature Medicine , the Bayer group even reports that its compounds reduce the number of sequelae—the subsequent outbreaks of sores after an initial infection.在四月性质医药拜耳集团的报告说,即使其化合物减少后遗症--随后爆发后初步成效感染.
"The unsolved problem of herpes infections, namely the sequelae, may become curable," says Kleymann."解决问题疱疹病毒,即后遗症,可能会成为治愈",kleymann.
Both research groups conclude that helicase-primase inhibitors are more potent than acyclovir and its derivatives.无论研究小组断定旋-引抑制剂更烈性比阿昔洛韦及其衍生物.
"People have been looking for years, and nobody had come up with anything that matches acyclovir," notes virologist Priscilla A. Schaffer of Harvard Medical School in Boston."多年来人们一直在寻找,无人出面凡是比赛阿昔洛韦"注病毒学家纪筠甲Schaffer在哈佛医学院波士顿. "These compounds are tremendously exciting.""这些都极大地振奋化合物"
At the moment, though, neither Bayer nor Boehringer Ingelheim plans to launch tests of helicase-primase inhibitors in people.目前,虽然也拜耳BoehringerIngelheim也计划发射试验旋-引抑制剂. "It's unfortunate because these compounds do look interesting, but companies have to make choices about what they are going to put their money and resources behind," says Paul Anderson, a vice president at Boehringer Ingelheim."这是不幸的事,因为这些化合物不看有趣但公司已经做出什么选择,他们将会把他们的资金和资源的背后的",保罗安德森、副院长于BoehringerIngelheim.
"The fundamental issue is that no pharmaceutical company wants to go head-to-head with acyclovir [and its derivatives]," says virologist Richard Whitley of the University of Alabama at Birmingham."根本的问题是,没有制药公司愿意再由头至头部阿昔洛韦〔及其衍生物]",病毒学家理查德说明该在阿拉巴马大学的伯明翰. "They do not see it as profitable.""他们不认为这是有利可图"
Both pharmaceutical firms say they hope to find other companies willing to finance further testing of their compounds.药厂说,他们都希望能找到其他公司愿意进一步测试其财务化合物.
"It's kind of depressing," notes Schaffer."这样令人沮丧,"注Schaffer. "We'd all love to see [a helicase-primase inhibitor] go into the clinic. One of these days, I dare say, it will.""我们都爱开玩笑地看到[旋-引抑制剂]走进诊所.有一天,我敢说,它将."
