Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses.,The Journal of Physical Chemistry Letters

当前位置： X-MOL 学术 › J. Phys. Chem. Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses.
The Journal of Physical Chemistry Letters ( IF 4.8 ) Pub Date : 2020-06-14 , DOI: 10.1021/acs.jpclett.0c01097
Cécilia Hognon ₁ , Tom Miclot _{1,

2} , Cristina Garcı A-Iriepa _{3,

4} , Antonio Francés-Monerris _{1,

5} , Stephanie Grandemange ₆ , Alessio Terenzi ₂ , Marco Marazzi _{3,

4} , Giampaolo Barone ₂ , Antonio Monari ₁

Affiliation

Coronaviruses may produce severe acute respiratory syndrome (SARS). As a matter of fact, a new SARS-type virus, SARS-CoV-2, is responsible for the global pandemic in 2020 with unprecedented sanitary and economic consequences for most countries. In the present contribution we study, by all-atom equilibrium and enhanced sampling molecular dynamics simulations, the interaction between the SARS Unique Domain and RNA guanine quadruplexes, a process involved in eluding the defensive response of the host thus favoring viral infection of human cells. Our results evidence two stable binding modes involving an interaction site spanning either the protein dimer interface or only one monomer. The free energy profile unequivocally points to the dimer mode as the thermodynamically favored one. The effect of these binding modes in stabilizing the protein dimer was also assessed, being related to its biological role in assisting the SARS viruses to bypass the host protective response. This work also constitutes a first step in the possible rational design of efficient therapeutic agents aiming at perturbing the interaction between SARS Unique Domain and guanine quadruplexes, hence enhancing the host defenses against the virus.

中文翻译：

RNA 鸟嘌呤四链体在有利于冠状病毒中 SARS 独特结构域二聚化中的作用。

冠状病毒可能会导致严重急性呼吸道综合症（SARS）。事实上，一种新的 SARS 型病毒 SARS-CoV-2 是 2020 年全球大流行的罪魁祸首，给大多数国家带来了前所未有的卫生和经济后果。在本论文中，我们通过全原子平衡和增强采样分子动力学模拟，研究了 SARS 独特结构域和 RNA 鸟嘌呤四链体之间的相互作用，这一过程涉及逃避宿主的防御反应，从而有利于人类细胞的病毒感染。我们的结果证明了两种稳定的结合模式，涉及跨越蛋白质二聚体界面或仅一个单体的相互作用位点。自由能曲线明确表明二聚体模式是热力学上最有利的模式。还评估了这些结合模式在稳定蛋白质二聚体方面的效果，这与其协助 SARS 病毒绕过宿主保护反应的生物学作用有关。这项工作也构成了合理设计有效治疗剂的第一步，旨在扰乱 SARS 独特结构域和鸟嘌呤四链体之间的相互作用，从而增强宿主对病毒的防御能力。

更新日期：2020-07-16

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11