乙型肝炎病毒衣壳功能调查可能导致新的治疗方法

StephenW

Investigation of Hepatitis B Virus Capsid Function Could Lead to New Therapies
Jennifer Barrett, Associate Editor
Publish Date: Tuesday, July 17, 2018

In hepatitis B, the capsid, or protein shell, encloses the virus’ genetic blueprint and drives the delivery of that blueprint to infect a host cell. Although researchers believe that the capsid is a promising therapeutic target for the infection, not much is understood about its functionality and influence on its environment.

A new study published in eLife provides insight into previously unknown details about the capsid that may have implications for the development of new drugs to treat the infection. Using computer simulations, researchers from the University of Delaware performed all-atom molecular dynamics simulations, which allowed them to study how the molecules carry out their functions.  

Previous studies have used experimental microscopes to study the capsid but have not been able to provide high-resolution images of the complex structure, according to the researchers. Simulations have given researchers a better look at the capsid and how it interacts with its surroundings.

Through simulation, the researchers found asymmetry in capsid shape, revealing a highly flexible structure that suggests its ability to squeeze through an opening into the nucleus of a cell the virus is infecting.

“We think that the capsid might need that ability to distort in order to correctly package its genetic blueprint and get it into the nucleus to generate new copies of the virus during the infection process,” Jodi A. Hadden, PhD, lead author of the study, said in a press release.

Knowing this detail could help lead to new drug treatments, according to the study. If the capsid could be made rigid and unable to distort, the infection process may be able to be stopped, the researchers noted.

Additionally, the researchers found that small triangular openings, or pores, in the surface of the capsid are likely where its protein “tails” poke through and send a signal that is essential to the infection process.

“We have all the details down to the atomic level,” Dr Hadden said. “You need that to develop a complete understanding of the molecule and to study drug interactions.”

The findings indicate that disruption of the capsid could be a promising approach to the development of new therapies for hepatitis B virus.

Reference

Hadden JA, Perilla JR, Schlicksup CJ, et al. All-atom molecular dynamics of the HBV capsid reveals insights into biological function and cryo-EM resolution limits. eLife. 2018. Doi: 10.7554/eLife.32478

StephenW

乙型肝炎病毒衣壳功能调查可能导致新的治疗方法
Jennifer Barrett，副主编
发布日期：2018年7月17日，星期二

在乙型肝炎中，衣壳或蛋白质壳包围病毒的基因蓝图并驱动该蓝图的传递以感染宿主细胞。虽然研究人员认为衣壳是一种很有前途的感染治疗靶点，但对其功能和对环境的影响知之甚少。

在eLife上发表的一项新研究提供了有关衣壳的先前未知细节的见解，这些细节可能对开发治疗感染的新药有影响。使用计算机模拟，来自特拉华大学的研究人员进行了全原子分子动力学模拟，这使他们能够研究分子如何发挥其功能。

研究人员表示，以前的研究已经使用实验显微镜研究衣壳，但未能提供复杂结构的高分辨率图像。模拟使研究人员更好地了解衣壳及其与周围环境的相互作用。

通过模拟，研究人员发现了衣壳形状的不对称性，揭示了一种高度灵活的结构，表明它能够通过一个开口进入病毒感染的细胞核。

“我们认为衣壳可能需要扭曲才能正确包装其基因蓝图并将其置于细胞核中以在感染过程中产生新的病毒拷贝，”Jodi A. Hadden，博士，主要作者研究在新闻发布会上说。

该研究表明，了解这一细节有助于开发新的药物治疗方法。研究人员指出，如果衣壳可以变得僵硬并且不能扭曲，那么感染过程可能会停止。

此外，研究人员发现，衣壳表面的小三角形开口或毛孔可能是其蛋白质“尾巴”刺穿并发出对感染过程至关重要的信号。

“我们将所有细节都归结为原子水平，”哈登博士说。 “你需要这样才能完全了解分子并研究药物相互作用。”

研究结果表明，破坏衣壳可能是开发乙型肝炎病毒新疗法的一种有前途的方法。

参考

Hadden JA，Perilla JR，Schlicksup CJ，et al。 HBV衣壳的全原子分子动力学揭示了对生物功能和低温EM分辨率限制的见解。网上生活。 2018. Doi：10.7554 / eLife.32478

Hepbest

期待