Mesoscopic view of spike glycoprotein inhibition by various size of fullerenes

Abstract

Fullerene molecules, a class of allotropic carbon nanomaterials, were investigated for their potential to inhibit SARS-CoV-2 by targeting its spike glycoprotein through molecular docking simulations. Both blind and targeted docking methods were employed to evaluate interactions between various fullerene sizes (C₂₀, C₂₈, C₆₀, C₇₈, C₈₄) and the spike glycoprotein. In the blind docking method, with the exception of C₈₄, all fullerene interactions are distributed over the entire surface of the spike glycoprotein. In the targeted docking method, C₇₈ and C₈₄ interactions are closer to the actual binding sites of angiotensin-converting enzyme 2 (ACE2) on the spike glycoprotein. The most negative binding affinity value was found for fullerene C₈₄, with a value of -15.9 kcal/mol, primarily via hydrophobic interactions. Binding affinity correlated positively with fullerene size; larger fullerenes demonstrated a greater capacity to obstruct the ACE2 binding site. Smaller fullerenes (C₂₀, C₂₈) were ineffective, binding at unrelated regions. C₆₀ showed moderate potential, with 85% of its binding occurring at the ACE2 site. In contrast, C₇₈ and C₈₄ exhibited 100% of their docking directly at the ACE2 binding site, indicating stronger inhibition potential. These findings underscore the significance of fullerene size in enhancing spike protein interaction and suggest that larger fullerenes, especially C₈₄, may serve as promising candidates for SARS-CoV-2 entry inhibition.