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具有对逃脱SARS-CoV-2变种增强中和效率的共价工程蛋白迷你结合剂

Yu Han^1,2, Zhenlin Yang^1,2, Hengrui Hu³

¹Synthetic and Functional Biomolecules Center, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Journal of the American Chemical Society

|February 25, 2022

概括

一种新的共价工程策略创建了有效中和SARS-CoV-2变种的蛋白质迷你结合剂. 这种方法提高了病毒进入的阻碍,为COVID-19治疗和预防提供了有前途的工具.

科学领域:

病毒学和免疫学
蛋白质工程
药物发现

背景情况:

新出现的 SARS-CoV-2 变种带有逃生突变对 COVID-19 控制构成重大挑战.
广泛中和试剂的开发对于有效的预防性和治疗性干预对进化的病毒株至关重要.

研究的目的:

开发一种对蛋白质微结合剂的共价工程策略,以中和SARS-CoV-2变种.
增强中和剂对抗像SARS-CoV-2这样快速演变的病毒的有效性.

主要方法:

蛋白质迷你结合剂是为了在现场与SARS-CoV-2尖端受体结合域 (RBD) 进行交叉结合而设计的.
评估了共价迷你结合剂 (GlueBinder) 的有效性,通过其阻断RBD与人类血管素转化酶2 (huACE2) 的相互作用.
对包括德尔塔在内的真实SARS-CoV-2变种的中和效应进行了评估.

主要成果:

与非共价形式相比,共价GlueBinder对RBD- huACE2相互作用的阻断得到了增强.
GlueBinder 显示出更强大的SARS-CoV-2 Delta 变种的中和作用.
这种策略在对抗德尔塔,卡帕和奥米克朗等变种方面表现出有效性.

结论:

蛋白迷你结合剂的共价工程为中和SARS-CoV-2逃生变体提供了强有力的策略.
这种方法提供了一种可通用的方法,用于恢复和增强中和剂对进化的病毒的有效性.
开发的GlueBinder代表了COVID-19治疗和预防治疗的有希望的候选者.

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