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

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 minutes. 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.

SUBMITTER: Kiew L

PROVIDER: S-EPMC8018905 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Real-time sensing of proteins, especially in wearable devices, remains a substantial challenge due to the need to convert a binding event into a measurable signal that is compatible with the chosen analytical instrumentation. Impedance spectroscopy enables real-time detection via either measuring electrostatic interactions or electron transfer reactions while simultaneously being amenable to miniaturization for integration into wearable form-factors. To create a more robust methodology for optimizing impedance-based sensors, additional fundamental studies exploring components influencing the design and implementation of these sensors are needed. This investigation addresses a sub-set of these issues by combining optical and electrochemical characterization to validate impedance-based sensor performance as a function of (1) biorecognition element density, (2) self-assembled monolayer chain length, (3) self-assembled monolayer charge density, (4) the electrochemical sensing mechanism and (5) the redox reporter selection. Using a pre-existing lysozyme aptamer and lysozyme analyte combination, we demonstrate a number of design criteria to advance the state-of-the-art in protein sensing. For this model system we demonstrated the following: First, denser self-assembled monolayers yielded substantially improved sensing results. Second, self-assembled monolayer composition, including both thickness and charge density, changed the observed peak position and peak current. Third, single frequency measurements, while less informative, can be optimized to replace multi-frequency measurements and in some cases (such as that with zwitterionic self-assembled monolayers) are preferred. Finally, various redox reporters traditionally not used in impedance sensing should be further explored. Collectively, these results can help limit bottlenecks associated with device development, enabling realization of next-generation impedance-based biosensing with customize sensor design for the specific application.

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

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