Modulating SARS-CoV-2 Spike Protein Reactivity through Moderate Electric Fields: A Pathway to Innovative Therapies

In the quest for effective COVID-19 treatments and vaccines, traditional biochemical methods have been paramount, yet the challenge of accommodating diverse viral mutants persists. Recent simulations propose an innovative physical strategy involving an external electric field applied to the SARS-CoV-2 spike protein, demonstrating a reduced viral binding potential. However, limited empirical knowledge exists regarding the characteristics of the spike protein after E-field treatment. Our study addresses this gap by employing diverse analytical techniques to elucidate the impact of low/moderate E-field intensity on the binding of the SARS-CoV-2 spike protein to the ACE2 receptor. Through comprehensive analysis, we unveil a substantial reduction in the spike protein binding capacity validated via enzyme-linked immunosorbent assay and quartz crystal microbalance experiments. Remarkably, the E-field exposure induces significant protein structure rearrangement, leading to an enhanced negative surface zeta potential confirmed by dynamic light scattering. Circular dichroism spectroscopy corroborates these structural changes, showing alterations in the secondary protein structures. This study provides insights into SARS-CoV-2 spike protein modification under an E-field pulse, potentially paving the way for nonbiochemical strategies to mitigate viral reactivity and opening avenues for innovative therapeutic and preventive approaches against COVID-19 and its evolving variants.