Life and Medical Sciences (LIMES), University of Bonn, Gerhard-Domagk-Str.1, 53121, Bonn, Germany.
Max Planck Fellow Chemical Biology, Center of Advanced European Studies and Research (caesar), Ludwig-Erhard-Allee 2, 53175, Bonn, Germany.
Angew Chem Int Ed Engl. 2021 Apr 26;60(18):10279-10285. doi: 10.1002/anie.202100316. Epub 2021 Mar 23.
The receptor binding domain (RBD) of the spike glycoprotein of the coronavirus SARS-CoV-2 (CoV2-S) binds to the human angiotensin-converting enzyme 2 (ACE2) representing the initial contact point for leveraging the infection cascade. We used an automated selection process and identified an aptamer that specifically interacts with CoV2-S. The aptamer does not bind to the RBD of CoV2-S and does not block the interaction of CoV2-S with ACE2. Nevertheless, infection studies revealed potent and specific inhibition of pseudoviral infection by the aptamer. The present study opens up new vistas in developing SARS-CoV2 infection inhibitors, independent of blocking the ACE2 interaction of the virus, and harnesses aptamers as potential drug candidates and tools to disentangle hitherto inaccessible infection modalities, which is of particular interest in light of the increasing number of escape mutants that are currently being reported.
冠状病毒 SARS-CoV-2（CoV2-S）的刺突糖蛋白的受体结合域（RBD）与人血管紧张素转换酶 2（ACE2）结合，代表着利用感染级联的初始接触点。我们使用自动选择过程鉴定了与 CoV2-S 特异性相互作用的适体。该适体不与 CoV2-S 的 RBD 结合，也不阻止 CoV2-S 与 ACE2 的相互作用。然而，感染研究表明，该适体可有效且特异性地抑制假病毒感染。本研究为开发 SARS-CoV2 感染抑制剂开辟了新的视野，无需阻断病毒与 ACE2 的相互作用，并利用适体作为潜在的药物候选物和工具来解开迄今为止难以接近的感染方式，鉴于目前正在报告的越来越多的逃逸突变体，这一点尤其重要。
