Electrochemical (EC) biosensors have emerged as promising platforms for detecting SARS-CoV-2 and its biomarkers. Strategies to provide selectivity and enhanced sensitivity include incorporating ligands on the sensor, which are typically modified through static covalent assemblies. Reversible Self-Assembled Monolayers (rSAMs), on the other hand, allow ligands to display lateral movement, a feature that mimics the multivalent recognition pattern occurring at the lipid bilayer on cell surfaces. Optical biosensors using this approach have demonstrated promising results for the detection of influenza viruses. This thesis work aimed to extend the use of rSAMs by introducing its concept in an electrochemical setting for the detection of the SARS-CoV-2 spike protein. The recognition element used was glycan-based, namely sialic acids, which was in the ωposition of benzamidine-terminated amphiphiles. Designed as a methodology development study, different redox couples (ferri-/ferrocyanide, ferrocene carboxylic acid, and ferrocene methanol), supporting solutions (PBS and HEPES), and electrodes (screenprinted gold electrodes (AuSPEs) and gold disc electrodes (GDEs)) were used. Infrared reflection adsorption spectroscopy (IRAS) was performed on model gold surfaces to ensure the stability of the rSAMs layer upon electrochemical measurements. According to IRAS data, the choice of electrolyte solution, in synergy with applied voltage, determines the stability of the rSAM, with ferrocene methanol (FcMe) in HEPES having the least effect on the rSAM composition. These findings align with the data from cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy. Herein, a successful voltammetric detection of SARS-CoV-2 spike protein at 10- and 20- nM concentrations using 0.5 mM FcMe in HEPES buffer on rSAMmodified GDEs is presented. Future work will be dedicated to validating these findings and to implement it on AuSPEs and wastewater systems. This work will thus highlight the potential of rSAMs in EC biosensing platforms for further studies.