Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors
Document Type
Article
Publication Date
7-1-2021
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film electrode as the core sensing element was fabricated for the screening of potential inhibitors against S-protein-ACE2 binding. The platform could detect interference of small analytes against S-protein-ACE2 binding at low analyte concentration and small volume (0.1 mu g/mL and similar to 1 mu L, estimated total analyte consumption < 4 pg) within 21 mM. Thus, a few potential inhibitors of S-protein-ACE2 binding were identified. This includes (25,3aS,6aS)-1-((S)-N-((S)-1-Carboxy-3-phenylpropyl)alanyl)tetrahydrocyc lopentab] pyrrole-2-carboxylic acid (ramiprilat) and (2S,3aS,7aS)-1-(2S)-2-(2S)-1-Carboxybutyl]amino]propanoyl]-2,3, 3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid (perindoprilat) that reduced the binding affinity of S-protein to ACE2 by 72% and 67%; and SARS-CoV-2 in vitro infectivity to the ACE2-expressing human oral cavity squamous carcinoma cells (OEC-M1) by 36.4 and 20.1%, respectively, compared to the PBS control. These findings demonstrated the usefulness of the developed biosensing platform for the rapid screening of modulators for S-protein-ACE2 binding.
Keywords
Palladium nano-thin-film electrode, Biosensor, Electrochemical impedance spectroscopy (EIS), ACE2-SARS CoV 2 S-Protein interaction, SARS-CoV-2 infection inhibitors
Divisions
fac_med
Funders
Ministry of Science and Technology (MOST), Taiwan (ROC) MOST 107-2112-M-009-016-MY3],Ministry of Science and Technology (MOST), Taiwan (ROC)[MOST 108-2314-B-006-009-MY3]16-MY3,Ministry of Science and Technology (MOST), Taiwan (ROC)[MOST 109-2327-B-010-005],Ministry of Science and Technology (MOST), Taiwan (ROC)[MOST 109-2327-B-009-001],Ministry of Science and Technology (MOST), Taiwan (ROC)[MOST 109-2327-B-182-002],Ministry of Science and Technology (MOST), Taiwan (ROC)[MOST 109-2927-I-009-003],Ministry of Education through the SPROUT Project,Center for Intelligent Drug Systems and Smart Biodevices (IDS2B) of NYCU, Taiwan
Publication Title
Biosensors & bioelectronics
Volume
183
Publisher
Elsevier Advanced Technology
Publisher Location
OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND