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

Lik Voon Kiew, Chia Yu Chang, Sheng Yu Huang, Pei Wen Wang, Choon Han Heh, Chung Te Liu, Chia Hsin Cheng, Yi Xiang Lu, Yen Chen Chen, Yi Xuan Huang, Sheng Yun Chang, Huei Yu Tsai, Yu An Kung, Peng Nien Huang, Ming Hua Hsu, Bey Fen Leo, Yiing Yee Foo, Chien Hao Su, Kuo Chen Hsu, Po Hsun HuangChirk Jenn Ng, Adeeba Kamarulzaman, Chiun Jye Yuan, Dar Bin Shieh, Shin Ru Shih, Lip Yong Chung, Chia Ching Chang

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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 μg/mL and ~1 μL, estimated total analyte consumption < 4 pg) within 21 min. Thus, a few potential inhibitors of S-protein-ACE2 binding were identified. This includes (2S,3aS,6aS)-1-((S)–N-((S)-1-Carboxy-3-phenylpropyl)alanyl)tetrahydrocyclopenta[b] 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.

Original languageEnglish
Article number113213
Number of pages10
JournalBiosensors and Bioelectronics
Publication statusPublished - 1 Jul 2021
Externally publishedYes


  • ACE2-SARS CoV 2 S-Protein interaction
  • Biosensor
  • Electrochemical impedance spectroscopy (EIS)
  • Palladium nano-thin-film electrode
  • SARS-CoV-2 infection inhibitors

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