A SARS-CoV-2 Spike Binding DNA Aptamer that Inhibits Pseudovirus Infection by an RBD-Independent Mechanism.

Abstract

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.

• Authors: Anton Schmitz, Anna Weber, Mehtap Bayin, Stefan Breuers, Volkmar Fieberg, Michael Famulok, Günter Mayer
• Journal: Angewandte Chemie (Weinheim an der Bergstrasse, Germany) (Angew Chem Weinheim Bergstr Ger) Vol. 133 Issue 18 Pg. 10367-10373 (Apr 26 2021) ISSN: 0044-8249 [Print] Germany
• PMID: 34230708 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.