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

https://doi.org/10.1016/j.bios.2021.113213Get rights and content
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Highlights

  • A sensitive sensing platform was developed to detect modulators that affect the SARS-CoV-2 and ACE2 interaction.

  • The modulators can be detected in a small volume of 1 μL with the total analyte consumption <4 pg.

  • The bio-probes can be conjugated to the flexible nano-Pd thin film electrode can be achieved within 15–20 min.

  • Potential leads, i.e., ramiprilat, and perindoprilat, that reduce the risks of the SARS-CoV-2 infection were identified.

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 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.

Keywords

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

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These authors contributed equally to this work.