Surface Activated Chemical Ionization – Cloud Ion Mobility Mass Spectrometry (SACI-CIMS) technology was used to separate low and high molecular weight ionic clusters to investigate the feasibility of electromagnetically inducing the modulation of the spike protein conformation. SACI-CIMS delivers a high throughput and a strong reduction in the ion trap space charge effect. Solvent clouds containing medium-high molecular weight protein ions were in-source selected and focused to the mass analyzer. Thanks to soft SACI ionization conditions - due to the low surface ionization potential (+/-47 V) - it was also possible to preserve the protein molecular structure and to perform interatomic studies (e.g.: protein-protein, protein analyte interactions). In this study, we investigated the spike glycoprotein and envelope protein of SARS-CoV-2 interaction with the mesenchymal cell membrane receptors under different chemical and physical conditions to better understand their impact on the protein expression. Thanks to the SACI-CIMS technology, we demonstrated electromagnetic frequency fieldsinduced conformational alterations of the spike protein, leading to protein denaturation. The magnitude of such effect was significantly augmented - up to 96% unfolding of the spike protein - when the protein was also exposed to Nacetylcysteine compounds