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SARS-CoV-2尖蛋白衍生周期性作为与GRP78的尖相互作用的调节器

Nicholas Johnson¹, Craig Pattinson², Kate Burgoyne²

¹Institute of Medical Sciences, University of Aberdeen, Ashgrove Road West, Aberdeen, AB25 2ZD, UK.

Chembiochem : a European journal of chemical biology

|April 13, 2024

概括

人类GRP78与SARS-CoV-2尖端蛋白结合. 针对这种相互作用的循环具有作为新型抗SARS-CoV-2药物的潜力,特别是那些来自Omicron变异的药物.

科学领域:

病毒学病毒学
分子生物学分子生物学
生物化学生物化学

背景情况:

人体葡萄糖调节蛋白GRP78是一种细胞伴侣,在压力条件下转移到细胞表面.
理论研究提出了GRP78在SARS-CoV-2病毒进入宿主细胞中的潜在作用.

研究的目的:

为了研究人类GRP78和SARS-CoV-2尖端蛋白之间的相互作用.
设计和评估来自SARS-CoV-2尖端蛋白变体的循环,以检测它们抑制这种相互作用的能力.

主要方法:

实验室表面等离子体共振 (SPR) 试验被用于确认人类GRP78与SARS-CoV-2尖端蛋白之间的结合.
循环是基于来自武汉和Omicron SARS-CoV-2变种的S1域的氨基酸循环结构 (480-488) 合成的.

主要成果:

人类GRP78被证实与SARS-CoV-2尖端蛋白结合.
武汉和Omicron衍生的循环都显示与GRP78.8结合.
与武汉衍生的相比,来自Omicron的呈现出较慢的解离动力学.
这两种循环都显著抑制了野生型S1蛋白与人类GRP78.8的结合.

结论:

人类GRP78是SARS-CoV-2尖端蛋白的直接结合伙伴.
针对GRP78-spike蛋白相互作用的设计周期性片显示出作为治疗剂的希望.
欧米克朗变异的结合特性表明,它有可能提高疗效,这需要进一步开发新的抗SARS-CoV-2策略.

关键词:

这就是BiP BiP BiP.循环类酸是一种循环类酸.在 GRP78 中使用.在HSPA5中,它是HSPA5的.这就是SARS-CoV-2病毒.

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