Interaction study of the ancestral and variants SARS-CoV-2 Spike protein with silver nanoparticle associated with the flavonoid hesperetin

• Grant number: 24/20500-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Collective Health - Epidemiology
• Principal Investigator: Ícaro Putinhon Caruso
• Grantee: Giulia Viana Dinis
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

The SARS-CoV-2 virus is the cause of the greatest recent global health emergency. It is of utmost importance to seek alternatives to minimize the impacts of this virus, since it still circulates among the population with high rates of mutability and transmission. Despite the current vaccines, it is necessary to incorporate technologies that make daily life safer in relation to SARS-CoV-2 and its variants. Among the possible structural targets to inhibit the activity of this virus, the Spike protein stands out, a trimeric glycoprotein presents in the viral membrane that is responsible for cell invasion through its binding to the ACE2 receptor. The search for ligands that interact with this protein and potentially prevent the infectious activity of the virus still presents itself as a key strategy. Silver nanoparticles (AgNP) have shown significant antiviral activity against SARS-CoV-2, inhibiting viral entry into the cell likely through binding to Spike. However, a molecular characterization of the Spike/AgNP interaction has not yet been reported. In this context, this project aims to characterize the interaction of ancestral and variant SARS-CoV-2 Spike proteins (D614G, Gamma, Delta, and Omicron) with AgNP associated with the flavonoid hesperetin (HSP), which showed a potent virucidal activity of 99.9% against betacoronaviruses. For that, UV-Vis absorption spectroscopy, circular dichroism, and Zeta potential techniques will be used to characterize the Spike/AgNP-HST complexes by determining dissociation constants, thermodynamic profile, electrostatic contribution, secondary structure change, and identification of the binding site. Therefore, this proposal may provide relevant molecular details for the development of new technologies to combat coronaviruses.