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
Publication Title
Biosensors & bioelectronics
Recommended Citation
Kiew, Lik-Voon; Chang, Chia-Yu; Huang, Sheng-Yu; Wang, Pei-Wen; Heh, Choon-Han; Liu, Chung-Te; Cheng, Chia-Hsin; Lu, Yi-Xiang; Chen, Yen-Chen; Huang, Yi-Xuan; Chang, Sheng-Yun; Tsai, Huei-Yu; Kung, Yu-An; Huang, Peng-Nien; Hsu, Ming-Hua; Leo, Bey-Fen; Foo, Yiing-Yee; Su, Chien-Hao; Hsu, Kuo-Chen; Huang, Po-Hsun; Ng, Chirk-Jenn; Kamarulzaman, Adeeba; Yuan, Chiun-Jye; Shieh, Dar-Bin; Shih, Shin-Ru; Chung, Lip-Yong; and Chang, Chia-Ching, "Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors" (2021). Research Publications (2021 to 2025). 12630.
https://knova.um.edu.my/research_publications_2021_2025/12630
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
Volume
183
Publisher
Elsevier Advanced Technology
Publisher Location
OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND