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ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Produce Safety and Microbiology Research » Research » Publications at this Location » Publication #418367
Research Project: Rapid Antemortem Tests for the Early Detection of Transmissible Spongiform Encephalopathies and Other Animal Diseases

Location: Produce Safety and Microbiology Research

Title: Elucidating the molecular docking and binding dynamics of aptamers with spike proteins across SARS-CoV-2 variants of concern

Author
item Quintela, Irwin
item VASSE, TYLER - Volunteer
item JIAN, DANA - Volunteer
item HARRINGTON, CAMERON - Former ARS Employee
item SIEN, WESLEY - Volunteer
item Wu, Vivian

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/29/2025
Publication Date: 2/14/2025
Citation: Quintela, I.A., Vasse, T., Jian, D., Harrington, C., Sien, W., Wu, V.C. 2025. Elucidating the molecular docking and binding dynamics of aptamers with spike proteins across SARS-CoV-2 variants of concern. Frontiers in Microbiology. 16. Article 1503890. https://doi.org/10.3389/fmicb.2025.1503890.
DOI: https://doi.org/10.3389/fmicb.2025.1503890

Interpretive Summary: In this report, DNA molecules or aptamers that specifically target and bind to the spike proteins of SARS-CoV-2 variants were generated. Both simulations and modeling using computer programs were applied on these aptamer sets to identify the sequences with the highest binding affinity toward spike proteins. Furthermore, analysis and characterization using fluorescence assay measured the stability and binding strength between aptamers and spike proteins which were in agreement with the simulation and modeling scores. As an excellent alternative to antibodies in the diagnostic field, the identified aptamer sequences can be further investigated for potential therapeutic and point-of-care test applications.

Technical Abstract: Highly specific DNA aptamers against SARS-CoV-2 spike proteins have been selected and analyzed. To better understand the binding affinities between DNA aptamers and spike proteins (S-proteins) of relevant variants of concerns (VOCs), in silico and in vitro characterization are excellent approaches to implement. Here, we identified and generated DNA aptamer sequences targeting the S-protein of SARS-CoV-2 VOCs through Systematic Evolution of Ligands by Exponential Enrichment (SELEX). In silico, prediction of aptamer binding was conducted, followed by a step-by-step workflow for secondary and tertiary aptamer structures determination, modeling, and molecular docking to target S-protein. The in silico strategy was limited to only providing predictions of possible outcomes based on scores, and ranking was complemented by characterization and analysis of identified DNA aptamers using a direct enzyme-linked oligonucleotides assay (ELONA) which showed an average dissociation constant (Kd) of < 50 nM at the low range across the three significant VOCs. These three highly specific VOCs aptamers can be further studied as potential candidates for both diagnostic and therapeutic applications.