Discovery and Characterization of Spike N-Terminal Domain-Binding Aptamers for Rapid SARS-CoV-2 Detection

Nataly Kacherovsky, Lucy F. Yang,Ha V. Dang, Emmeline L. Cheng, Ian I. Cardle, Dr. Alexandra C. Walls, Dr. Matthew McCallum, Prof. Drew L. Sellers, Prof. Frank DiMaio, Prof. Stephen J. Salipante, Dr. Davide Corti, Prof. David Veesler, Prof. Suzie H. Pun

Angewandte Chemie International Edition, Volume 60, Issue 39, Sept. 20, 2021

DOI: https://doi.org/10.1002/anie.202107730

Image abstract: Rapid diagnostics are essential for early detection of COVID-19 and reduced disease spread. In this study, we discovered the DNA aptamer SNAP1 (SARS-CoV-2 spike protein N-terminal domain binding aptamer 1), which binds with high affinity and specificity to SARS-CoV-2 spike protein as well as UV-inactivated SARS-CoV-2 virus.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has devastated families and disrupted healthcare, economies and societies across the globe. Molecular recognition agents that are specific for distinct viral proteins are critical components for rapid diagnostics and targeted therapeutics. In this work, we demonstrate the selection of novel DNA aptamers that bind to the SARS-CoV-2 spike glycoprotein with high specificity and affinity (<80?nM). Through binding assays and high resolution cryo-EM, we demonstrate that SNAP1 (SARS-CoV-2 spike protein N-terminal domain-binding aptamer 1) binds to the S N-terminal domain. We applied SNAP1 in lateral flow assays (LFAs) and ELISAs to detect UV-inactivated SARS-CoV-2 at concentrations as low as 5×10⁵?copies?mL^?1. SNAP1 is therefore a promising molecular tool for SARS-CoV-2 diagnostics.