毒品攻击乙型肝炎病毒衣壳

StephenW

Drug Attacks Hepatitis B Virus Capsid
Laurie Toich, Associate Editor
Publish Date: Wednesday, February 21, 2018

Researchers have recently made progress in developing new drugs to combat hepatitis B virus (HBV), according to a new study published by eLife.

Billions of individuals worldwide have been infected with HBV and millions are living with a chronic infection. Despite the creation of a vaccine, there is no cure for the liver disease.

In the new study, the researchers were able to determine how HBV changes its structure when it binds with an experimental antiviral drug currently being explored in clinical trials.

"Our discovery suggests that this same drug could attack hepatitis B virus on multiple fronts—both preventing replication and killing new copies of the virus," said senior author Adam Zlotnick, PhD. "If we're smart, we can take advantage of the multiple ways this drug can work at the same time."

Viruses replicate by hijacking a cell to produce more of the virus and protect its DNA and RNA by containing it in a capsid. The research team focused on studying the physics of how capsids are formed.

"The reaction is a bit like throwing a deck of cards in the air to build the Taj Mahal -- a highly complex structure seemingly emerging from chaos," Dr Zlotnick said.

The authors previously discovered a class of molecules that disrupt capsid protein assembly, called core protein allosteric modulators (CpAMs).

CpAM molecules cause the shells of viruses to assemble incorrectly, thus altering the life cycle of the virus; however, CpAMs were thought to only disrupt capsid formation after its DNA was already protected.

The new findings suggest that molecules can break apart the capsid after it has already been formed, according to the authors.

"The big implication is viral capsids aren't as impenetrable as previously thought," Dr Zlotnick said. “The other implication, which may be even more important, is that if this type of interference works against hepatitis B virus, it might also work against other viruses.”

Through cryo-electron microscopy, the researchers discovered that the CpAM molecule was able to bend and distort the “soccer ball-shaped” capsid, according to the study.

Although this molecule is not included in ongoing clinical trials of CpAMs, these findings highlight the potential therapeutic power of the drug class, according to the study. The authors said they plan to conduct similar trials of this molecule in the future.

"About half of known virus families have soccer ball-like capsids; examples include polio and herpes," Dr Zlotnick said. "This study may lead to better treatments against them since the mechanisms behind capsid disruption could lead to drugs against any of them."

StephenW

毒品攻击乙型肝炎病毒衣壳
Laurie Toich，副编辑
发布日期：2018年2月21日，星期三

根据eLife发布的一项新研究，研究人员最近在开发用于抗乙型肝炎病毒（HBV）的新药方面取得了进展。

全球数十亿人感染了HBV，数百万人患有慢性感染。尽管已经开发出疫苗，但对肝脏疾病没有治愈的办法。

在新的研究中，研究人员能够确定当HBV与目前正在临床试验中探索的实验性抗病毒药物结合时，HBV如何改变其结构。

资深作者Adam Zlotnick博士说：“我们的发现表明，这种相同的药物可以在多个方面攻击乙型肝炎病毒，既能防止复制又能杀死病毒的新副本。 “如果我们很聪明，我们可以利用这种药物可以同时工作的多种方式。”

病毒通过劫持细胞产生更多的病毒并通过将其包含在衣壳中来保护其DNA和RNA而复制。研究小组专注于研究衣壳形成的物理学。

“这种反应有点像在空中投掷一副牌来建造泰姬陵 - 这是一个看起来从混乱中出现的非常复杂的结构，”Zlotnick博士说。

作者以前发现了一类破坏衣壳蛋白组装的分子，称为核心蛋白质变构调节剂（CpAMs）。

CpAM分子导致病毒的外壳组装不正确，从而改变病毒的生命周期;然而，CpAM被认为只在DNA已被保护后才破坏衣壳的形成。

这组作者说，新的发现表明，分子可以在衣壳已经形成之后将衣壳分开。

“这意味着病毒衣壳并不像以前想象的那样难以穿透，”Zlotnick博士说。 “另一个可能更重要的含义是，如果这种类型的干扰对抗乙型肝炎病毒，它可能也会对付其他病毒。”

根据研究，通过低温电子显微镜，研究人员发现CpAM分子能弯曲和扭曲“足球形”衣壳。

研究表明，虽然这种分子不包括在正在进行的CpAMs临床试验中，但这些研究结果强调了该类药物的潜在治疗功效。作者说他们计划在未来对这种分子进行类似的试验。

“大约有一半的已知病毒家族有足球样的衣壳，例子包括小儿麻痹症和疱疹，”Zlotnick博士说。 “这项研究可能会导致更好的治疗方法，因为衣壳破裂后的机制可能会导致药物对其中的任何一种。”

V友

CpAM分子导致病毒的外壳组装不正确，从而改变病毒的生命周期

StephenW

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Zlotnick博士是Assembly生物技术的创始人, 一个关于衣壳研究的权威.

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