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Advances in Magnetic Microbead Affinity Selection Screening: Discovery of Natural Ligands to the SARS-CoV-2 Spike Protein
- Source :
- J Am Soc Mass Spectrom
- Publication Year :
- 2021
- Publisher :
- American Chemical Society (ACS), 2021.
-
Abstract
- Affinity selection-mass spectrometry, which includes magnetic microbead affinity selection-screening (MagMASS), is ideal for the discovery of ligands in complex mixtures that bind to pharmacological targets. Therapeutic agents are needed to prevent or treat COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection of human cells by SARS-CoV-2 involves binding of the virus spike protein subunit 1 (S1) to the human cell receptor angiotensin converting enzyme-2 (ACE2). Like antibodies, small molecules have the potential to block the interaction of the viral S1 protein with human ACE2 and prevent SARS-CoV-2 infection. Therefore, a MagMASS assay was developed for the discovery of ligands to the S1 protein. Unlike previous MagMASS approaches, this new assay used robotics for five-fold enhancement of throughput and sensitivity. The assay was validated using the SBP-1 peptide, which is identical to the ACE2 amino acid sequence recognized by the S1 protein, and then applied to the discovery of natural ligands from botanical extracts. Small molecule ligands to the S1 protein were discovered in extracts of the licorice species, Glycyrrhiza inflata. In particular, the licorice ligand licochalcone A was identified through dereplication and comparison with standards using HPLC with high-resolution tandem mass spectrometry.
- Subjects :
- Binding Sites
SARS-CoV-2
Drug Evaluation, Preclinical
COVID-19
Fabaceae
Ligands
Antiviral Agents
Article
Mass Spectrometry
COVID-19 Drug Treatment
Molecular Docking Simulation
Chalcones
Structural Biology
Drug Discovery
Spike Glycoprotein, Coronavirus
Humans
Angiotensin-Converting Enzyme 2
Spectroscopy
Protein Binding
Subjects
Details
- ISSN :
- 18791123 and 10440305
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society for Mass Spectrometry
- Accession number :
- edsair.doi.dedup.....002cc599086370d7d36d43618def3236