在GRP78-SARS-CoV-2接口的GRP78上确定一个可用药物的位置,并对化合物进行虚拟查以破坏该接口

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Maria Lazou¹, Jonathan R Hutton¹, Arijit Chakravarty²

¹Department of Biomedical Engineering, Boston University, Boston, MA, 02215, USA.

Journal of computer-aided molecular design

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概括

针对GRP78的新型抗病毒药物可以阻止SARS-CoV-2进入细胞. 这种方法为疫苗提供了替代方案,并可能有助于对抗病毒进化和新兴变异.

科学领域:

病毒学病毒学
结构生物学结构生物学
药物发现药物发现药物发现

背景情况:

SARS-CoV-2 导致COVID-19,这是一个全球性流行病,正在不断出现变种.
目前的疫苗针对的是尖蛋白,驱动病毒免疫逃避.
针对像GRP78这样的宿主因子的抗病毒药物可以提供直角选择压力.

研究的目的:

通过向GRP78宿主因子来确定针对SARS-CoV-2的新型治疗策略.
开发GRP78-Spike RBD-ACE2复合物的分子模型.
发现破坏GRP78与SARS-CoV-2尖端蛋白之间的相互作用的小分子.

主要方法:

开发了GRP78-Spike RBD-ACE2复合体的结构模型.
使用热点映射来确定GRP78.8上的尖端蛋白结合点.
对药物库进行了基于结构的虚拟选,针对GRP78.8.

主要成果:

在GRP78.8上确定了SARS-CoV-2尖端蛋白的潜在结合部位.
发现的候选药物预计会破坏GRP78-spike蛋白相互作用.
一个已识别的化合物的子集显示了对SARS-CoV-2的先前活性.

结论:

GRP78是一种可行的药物标,可以抑制SARS-CoV-2的进入.
破坏GRP78-spike蛋白复合体提供了一个有前途的治疗策略.
这种方法可能会导致SARS-CoV-2和潜在的其他病毒感染的新疗法.

关键词:

在 COVID-19 疫情中,热点识别热点识别分子对接是分子对接.蛋白质蛋白质相互作用

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