TitleAdvances in Magnetic Microbead Affinity Selection Screening: Discovery of Natural Ligands to the SARS-CoV-2 Spike Protein.
Publication TypeJournal Article
Year of Publication2022
AuthorsMuchiri RN, Kibitel J, Redick MA, van Breemen RB
JournalJ Am Soc Mass Spectrom
Date Published2022 Jan 05
KeywordsAngiotensin-Converting Enzyme 2, Antiviral Agents, Binding Sites, Chalcones, COVID-19, COVID-19 Drug Treatment, Drug Discovery, Drug Evaluation, Preclinical, Fabaceae, Humans, Ligands, Mass Spectrometry, Molecular Docking Simulation, Protein Binding, SARS-CoV-2, Spike Glycoprotein, Coronavirus

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 5-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, . In particular, the licorice ligand licochalcone A was identified through dereplication and comparison with standards using HPLC with high-resolution tandem mass spectrometry.

Alternate JournalJ Am Soc Mass Spectrom
PubMed ID34939787
PubMed Central IDPMC9429804
Grant ListT32 AT010131 / AT / NCCIH NIH HHS / United States