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A SARS-CoV-2 Spike Binding DNA Aptamer that Inhibits Pseudovirus Infection by an RBD-Independent Mechanism*
Anton Schmitz1,2, Anna Weber1,3, Mehtap Bayin1,2
1Life and Medical Sciences (LIMES), University of Bonn, Gerhard-Domagk-Str.1, 53121, Bonn, Germany.
Angewandte Chemie (International Ed. in English)
|March 8, 2021
Summary
A novel aptamer effectively inhibits SARS-CoV-2 pseudoviral infection without blocking ACE2 interaction. This discovery offers new strategies for developing SARS-CoV-2 inhibitors and understanding viral entry mechanisms.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- The SARS-CoV-2 spike glycoprotein's receptor binding domain (RBD) binds ACE2, initiating viral infection.
- Developing effective SARS-CoV-2 inhibitors is crucial, especially with emerging escape mutants.
Purpose of the Study:
- To identify and characterize novel aptamers targeting SARS-CoV-2.
- To investigate the inhibitory potential of a newly identified aptamer against SARS-CoV-2 pseudoviral infection.
- To explore alternative mechanisms for SARS-CoV-2 inhibition beyond ACE2 blockade.
Main Methods:
- Automated aptamer selection process.
- Binding assays to assess aptamer interaction with CoV2-S RBD and ACE2.
- Pseudoviral infection studies to evaluate aptamer efficacy.
Main Results:
- An aptamer was identified that specifically interacts with CoV2-S.
- The aptamer does not bind to the CoV2-S RBD or block CoV2-S/ACE2 interaction.
- The aptamer demonstrated potent and specific inhibition of pseudoviral infection.
Conclusions:
- Aptamers can inhibit SARS-CoV-2 infection through mechanisms independent of ACE2 binding.
- This study presents aptamers as promising drug candidates for SARS-CoV-2.
- The findings provide new tools for studying viral infection pathways and developing strategies against resistant mutants.
