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Enhanced susceptibility of SARS-CoV-2 spike RBD protein assay targeted by cellular receptors ACE2 and CD147: Multivariate data analysis of multisine impedimetric response

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of spike protein to the host cell surface-expressing angiotensin-converting enzyme 2 (ACE2) or by endocytosis mediated by extracellular matrix metalloproteinase inducer (CD147). We present extended stat...

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Detalles Bibliográficos
Autores principales: Brodowski, Mateusz, Pierpaoli, Mattia, Janik, Monika, Kowalski, Marcin, Ficek, Mateusz, Slepski, Pawel, Trzaskowski, Bartosz, Swain, Greg, Ryl, Jacek, Bogdanowicz, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier B.V. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327189/
https://www.ncbi.nlm.nih.gov/pubmed/35911567
http://dx.doi.org/10.1016/j.snb.2022.132427
Descripción
Sumario:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of spike protein to the host cell surface-expressing angiotensin-converting enzyme 2 (ACE2) or by endocytosis mediated by extracellular matrix metalloproteinase inducer (CD147). We present extended statistical studies of the multisine dynamic electrochemical impedance spectroscopy (DEIS) revealing interactions between Spike RBD and cellular receptors ACE2 and CD147, and a reference anti-RBD antibody (IgG2B) based on a functionalised boron-doped diamond (BDD) electrode. The DEIS was supported by a multivariate data analysis of a SARS-CoV-2 Spike RBD assay and cross-correlated with the atomic-level information revealed by molecular dynamics simulations. This approach allowed us to study and detect subtle changes in the electrical properties responsible for the susceptibility of cellular receptors to SARS-CoV-2, revealing their interactions. Changes in electrical homogeneity in the function of the RBD concentration led to the conclusion that the ACE2 receptor delivers the most homogeneous surface, delivered by the high electrostatic potential of the relevant docking regions. For higher RBD concentrations, the differences in electrical homogeneity between electrodes with different receptors vanish. Collectively, this study reveals interdependent virus entry pathways involving separately ACE2, CD147, and spike protein, as assessed using a biosensing platform for the rapid screening of cellular interactions (i.e. testing various mutations of SARS-CoV-2 or screening of therapeutic drugs).