Biophysical studies of the interaction of hRSV Non-Structural 1 protein with natural flavonoids and their acetylated derivatives by spectroscopic techniques and computational simulations

Author(s)

de Lourenco, Isabella Ottenio ; Quintino, Evelyn Toscano Pedroso ; Pereira, Matheus Henrique ; Lima, Caroline Sprengel ; Araujo, Gabriela Campos ; Regasini, Luis Octavio ; Melo, Fernando Alves de ; Souza, Fatima Pereira de ; Fossey, Marcelo Andres ; Caruso, Icaro Putinhon

• Document type: Journal article
• Source: SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY; v. 283, p. 12-pg., 2022-08-13.

Abstract

Human respiratory syncytial virus (hRSV) infections are one of the most causes of acute lower respiratory tract infections in children and elderly. The development of effective antiviral therapies or preventive vaccines against hRSV is not available yet. Thus, it is necessary to search for protein targets to combat this viral infection, as well as potential ways to block them. Non-Structural 1 (NS1) protein is an important factor for viral replication success since reduces the immune response by interacting with proteins in the type I interferon pathway. The influence of NS1 on the cell's immune response denotes the potential of its inhibition, being a possible target of treatment against hRSV infection. Here, it was studied the interaction of hRSV NS1 with natural flavonoids chrysin, morin, kaempferol, and myricetin and their mono-acetylated chrysin and penta-acetylated morin de-rivatives using spectroscopic techniques and computational simulations. The fluorescence data indicate that the binding affinities are on the order of 105 M-1, which are directly related to the partition coefficient of each flavonoid with Pearson's correlation coefficients of 0.76-0.80. The thermodynamic analysis suggests that hy-drophobic interactions play a key role in the formation of the NS1/flavonoid complexes, with positive values of enthalpy and entropy changes. The computational approach proposes that flavonoids bind in a region of NS1 formed between the C-terminal alpha 3-helix and the protein core, important for its biological function, and corroborate with experimental data revealing that hydrophobic contacts are important for the binding. There-fore, the present study provides relevant molecular details for the development of a possible new strategy to fight infections caused by hRSV. (AU)

• FAPESP's process: 13/24355-2 - Cloning, expression and analysis of the interaction of the M2-1 protein of HRSV with Flavonides: investigation for targets in blocking viral replication
• Grantee: Fátima Pereira de Souza
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/18169-3 - Investigations of physical chemistry processes related with the binding of environmental relevant heavy metal ions by calix[4]arenes using molecular dynamics simulations
• Grantee: Alexandre Suman de Araujo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/18868-2 - Multi-user equipment acquisition for molecular and structural biology
• Grantee: Raghuvir Krishnaswamy Arni
• Support Opportunities: Multi-user Equipment Program