Coronaviruses may produce severe acute respiratory syndrome (SARS). Indeed, a new SARS-type virus, SARS-CoV-2, is responsible of a global pandemic in 2020 with unprecedented sanitary and economic consequences for most countries. In the present contribution we study, by using 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. Results evidence two stable binding modes with guanine quadruplexes, driven either by electrostatic (dimeric mode) or dispersion (monomeric mode) interactions, are proposed being the dimeric mode the preferred one as observed by their corresponding free energy surfaces. The effect of these binding modes in stabilizing the protein dimer is also assessed, since they are related to its biological role in assisting SARS viruses to escape 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：

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RNA鸟嘌呤四链体在冠状病毒中促进SARS独特域二聚化的作用

冠状病毒可能产生严重的急性呼吸道综合症（SARS）。确实，一种新的SARS型病毒SARS-CoV-2导致2020年的全球大流行，对大多数国家造成了前所未有的卫生和经济后果。在当前的贡献中，我们通过使用全原子平衡和增强的采样分子动力学模拟来研究SARS独特结构域与RNA鸟嘌呤四链体之间的相互作用，该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。结果证明，通过静电（二聚体模式）或分散体（单体模式）相互作用驱动的鸟嘌呤四链体的两种稳定结合模式被提出为二聚体模式，从其相应的自由能表面观察，这是优选的一种。还评估了这些结合方式在稳定蛋白质二聚体中的作用，因为它们与协助SARS病毒逃脱宿主保护性反应的生物学作用有关。这项工作还构成了可能的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。