Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors

Kiew, Lik-Voon and Chang, Chia-Yu and Huang, Sheng-Yu and Wang, Pei-Wen and Heh, Choon-Han and Liu, Chung-Te and Cheng, Chia-Hsin and Lu, Yi-Xiang and Chen, Yen-Chen and Huang, Yi-Xuan and Chang, Sheng-Yun and Tsai, Huei-Yu and Kung, Yu-An and Huang, Peng-Nien and Hsu, Ming-Hua and Leo, Bey-Fen and Foo, Yiing-Yee and Su, Chien-Hao and Hsu, Kuo-Chen and Huang, Po-Hsun and Ng, Chirk-Jenn and Kamarulzaman, Adeeba and Yuan, Chiun-Jye and Shieh, Dar-Bin and Shih, Shin-Ru and Chung, Lip-Yong and Chang, Chia-Ching (2021) Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors. Biosensors & bioelectronics, 183. ISSN 0956-5663, DOI https://doi.org/10.1016/j.bios.2021.113213.

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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.

Item Type: Article
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
Uncontrolled Keywords: Palladium nano-thin-film electrode;Biosensor; Electrochemical impedance spectroscopy (EIS);ACE2-SARS CoV 2 S-Protein interaction;SARS-CoV-2 infection inhibitors
Subjects: Q Science > QC Physics
R Medicine
T Technology > TP Chemical technology
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 31 May 2022 06:37
Last Modified: 31 May 2022 06:37
URI: http://eprints.um.edu.my/id/eprint/34622

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