Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
ChemMedChem. 2022 Jul 5;17(13):e202200166. doi: 10.1002/cmdc.202200166. Epub 2022 May 31.
Aptamers that can recognize the spike (S) protein of SARS-CoV-2 with high affinity and specificity are useful molecules towards the development of diagnostics and therapeutics to fight COVID-19. However, this S protein is constantly mutating, producing variants of concern (VoCs) that can significantly weaken the binding by aptamers initially engineered to recognize the S protein of the wildtype virus or a specific VoC. One strategy to overcome this problem is to develop universal aptamers that are insensitive to all or most of the naturally emerging mutations in the protein. We have recently demonstrated this concept by subjecting a pool of S protein-binding DNA aptamers for one-round parallel-SELEX experiments targeting 5 different S protein variants for binding-based sequence enrichment, followed by bioinformatic analysis of the enriched pools. This effort has led to the identification of a universal aptamer that recognizes 8 different variants of the spike protein with equally excellent affinity.
与 SARS-CoV-2 的刺突 (S) 蛋白具有高亲和力和特异性的适体是开发用于对抗 COVID-19 的诊断和治疗方法的有用分子。然而，这种 S 蛋白不断发生突变，产生令人关注的变异体 (VoC)，这些变异体可能会显著削弱最初设计用于识别野生型病毒或特定 VoC 的 S 蛋白的适体的结合。克服这个问题的一种策略是开发对该蛋白中所有或大多数自然出现的突变都不敏感的通用适体。我们最近通过对针对 5 种不同 S 蛋白变异体的一轮平行 SELEX 实验中针对 5 种不同 S 蛋白变异体进行了一轮平行 SELEX 实验，进行了这一概念的验证，实验目的是基于结合的序列富集，然后对富集的池进行生物信息学分析。这项工作已经鉴定出一种通用适体，它可以同等优异的亲和力识别 8 种不同的刺突蛋白变异体。
