《抗菌剂与化疗》：新化合物可杀死艾滋病病毒

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据美国物理学家组织网11月24日报道，美国科学家发现了一种能破坏艾滋病病毒（HIV）的新化合物PD 404182，测试结果显示，这种小分子化合物能在HIV感染细胞之前将病毒杀死，从而可预防人类罹患和传播艾滋病。最新研究发表在11月份出版的美国微生物学会会刊《抗菌剂与化疗》期刊网络版上。

德州农机大学阿蒂麦克菲林化学工程系的副教授陈之蕾（音译）领导的科研团队和斯克利普斯研究所的科学家，在筛选可对付丙型肝炎病毒（HCV）的药物的过程中意外发现了该化合物的。他们使用陈之蕾研发的一套筛查系统，筛查了数千种分子化合物，希望能“揪出”阻止HCV作乱的分子。结果发现，PD 404182不仅可抑制HCV病毒作乱，也对慢病毒起作用。随后，他们用同为慢病毒的HIV进行测试后发现，这种化合物对HIV比对HCV更有效。

最重要的是，PD 404182具有非常独特的作用机制，其杀死病毒是通过作用于病毒内的某些物质而非有毒的包膜蛋白，这意味着，在该化合物对付HIV时，HIV无法修改蛋白以增强抵抗力，而通过修改蛋白来增强抵抗力正是HIV非常难对付的原因之一。现在已知的抗病毒化合物都会同病毒膜相互作用，但PD 404182会避免与病毒膜相互作用。这一点非常重要，因为人的细胞也拥有同样的细胞膜，能破坏病毒膜的化合物也能破坏并最终杀死人的细胞，因此，不同细胞膜作用的PD 404182非常适用于对人进行临床治疗。
尽管这种化合物目前还无法用于治疗艾滋病，但其具有巨大的潜力，可用于预防艾滋病并阻断HIV在人与人之间的传播。”陈之蕾说。不过，她也强调，这种具有巨大的潜力化合物破坏HIV的机制还有待进一步研究，另外，同化学家合作改进其效果也非常必要。（来源：科技日报 刘霞）

PD 404,182 is a virucidal small molecule that disrupts hepatitis C virus and human immunodeficiency virus

We describe a virucidal small molecule, PD 404,182, effective against hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The median IC50 values for the antiviral effect of PD 404,182 against HCV and HIV in cell culture are 11 μM and 1 μM, respectively. The antiviral activity of PD 404,182 is due to physical disruption of virions that is accompanied to varying degrees (depending on the virus and exposure temperature/time) by release of viral nucleic acids into the surrounding medium. PD 404,182 does not directly lyse liposomal membranes even after extended exposure and shows no attenuation in antiviral activity when pre-incubated with liposomes of various lipid compositions, suggesting that the compound inactivates viruses through interaction with a non-lipid structural component of the virus. The virucidal activity of PD 404,182 appears to be virus-specific as little to no viral inactivation was detected with the enveloped Dengue and Sindbis viruses. PD 404,182 effectively inactivates a broad range of primary isolates of HIV-1 as well as HIV-2 and simian immunodeficiency virus (SIV), and does not exhibit significant cytotoxicity with multiple human cell lines in vitro (CC50 > 300 μM). The compound is fully active in cervical fluids although exhibiting decreased potency in the presence of human serum, retains its full antiviral potency for over 8 h when in contact with cells and is effective against both cell-free and cell-associated HIV. These qualities make PD 404,182 an attractive candidate microbicide for the prevention of HIV transmission through sexual intercourse.


作 者：Ana Maria Chamouna, Karuppiah Chockalingama, Michael Bobardtc, Rudo Simeona, Jinhong Changd, Philippe Gallayc,1 and Zhilei Chena,b,1
期刊名称： Antimicrobial Agents and Chemotherapy
期卷页： 第卷 第期 页 原文链接：http://aac.asm.org/content/early/2011/11/10/AAC.05722-11.abstract?sid=d38ce85f-1954-474c-a963-c6564fa8a27a