Department of Bioengineering, University of Washington, Seattle, Washington 98195, United States.
Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, United States.
Anal Chem. 2022 Sep 20;94(37):12683-12690. doi: 10.1021/acs.analchem.2c01993. Epub 2022 Aug 16.
During the COVID-19 (coronavirus disease 2019) pandemic, several SARS-CoV-2 variants of concern emerged, including the Omicron variant, which has enhanced infectivity and immune invasion. Many antibodies and aptamers that bind the spike (S) of previous strains of SARS-CoV-2 either do not bind or bind with low affinity to Omicron S. In this study, we report a high-affinity ARS-oV-2 micron BD-binding aptamr (SCORe) that binds Omicron BA.1 and BA.2 RBD with nanomolar . We employ aptamers SCORe.50 and SNAP4.74 in a multiplexed lateral flow assay (LFA) to distinguish between Omicron and wild-type S at concentrations as low as 100 pM. Finally, we show that SCORe.50 and its dimerized form SCOReD can neutralize Omicron S-pseudotyped virus infection of ACE2-overexpressing cells by >70%. SCORe therefore has potential applications in COVID-19 rapid diagnostics as well as in viral neutralization.
在 COVID-19(冠状病毒病 2019)大流行期间,出现了几种令人关注的 SARS-CoV-2 变体,包括具有增强传染性和免疫入侵能力的奥密克戎变体。许多与以前的 SARS-CoV-2 株的刺突(S)结合的抗体和适体要么不与奥密克戎 S 结合,要么结合亲和力低。在这项研究中,我们报告了一种高亲和力的 ARS-oV-2 微 BD 结合适体(SCORe),它以纳摩尔级亲和力结合奥密克戎 BA.1 和 BA.2 RBD。我们在多重侧向流动测定(LFA)中使用适体 SCORe.50 和 SNAP4.74 来区分奥密克戎和野生型 S,浓度低至 100 pM。最后,我们表明 SCORe.50 及其二聚体形式 SCOReD 可以中和 ACE2 过表达细胞中奥密克戎 S-假型病毒感染超过 70%。因此,SCORe 具有在 COVID-19 快速诊断以及病毒中和方面的潜在应用。