Enhanced Susceptibility of SARS-CoV-2 Spike RBD Protein Assay Targeted by Cellular Receptors ACE2 and CD147: Multivariate Data Analysis of Multisine Impedimetric Response

Abstract

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. Our 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 paths involving separately ACE2, CD147, and spike protein, provided by a developed biosensing platform for the rapid screening of cellular interactions (i.e. testing various mutations of SARS-CoV-2 or screening of therapeutic drugs).

Note:
Funding Information: This work was supported by the National Science Centre (Republic of Poland) under projects 2020/01/0/ST7/00104 (R.B.) and 2020/37/B/ST7/03262 (J.R.). M.J. acknowledge the support from the Foundation for Polish Science within START 2021 program. Molecular modelling was performed on the Okeanos HPC at the Interdisciplinary Centre for Mathematical and Computational Modelling within the g86-1058 and g87-1079 grants.

Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Keywords: SARS-CoV-2, Immunosensor, impedance monitoring, ACE2, CD147, multivariate statistical analysis