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

• Main Authors: 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, Chang, Chia-Ching
• Format: Article
• Published: Elsevier Advanced Technology 2021
• Subjects: QC Physics; R Medicine; TP Chemical technology
• Online Access: http://eprints.um.edu.my/34622/
• Institution: Universiti Malaya

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.