Interaction of Human Respiratory Syncytial Virus (HRSV) Matrix Protein with Resveratrol Shows Antiviral Effect

Author(s)

Rodrigues, Thaina ; Busso, Jefferson de Souza ; Dias, Raphael Vinicius Rodrigues ; Lourenco, Isabella Ottenio ; de Sa, Jessica Marostica ; de Carvalho, Sidney Jurado ; Caruso, Icaro Putinhon ; Souza, Fatima Pereira de ; Fossey, Marcelo Andres

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 25, n. 23, p. 14-pg., 2024-12-01.

Abstract

The respiratory syncytial virus (RSV) matrix protein plays key roles in the virus life cycle and is essential for budding, as it stimulates the optimal membrane curvature necessary for the emergence of viral particles. Resveratrol, a polyphenol (3,4 ',5-trihydroxy-trans-stilbene) produced by plants, exhibits pharmacological effects, including anti-inflammatory and antiviral activities. In this study, resveratrol was tested in HEp-2 (Epidermoid carcinoma of the larynx cell) cells for its post-infection effects, and recombinant M protein was produced to characterize the biophysical mechanisms underlying this interaction. The CC50 (Cytotoxic concentration 50%) value for resveratrol was determined to be 297 mu M over 48 h, and the results from the HEp-2 cell cultures demonstrated a viral inhibition of 42.7% in the presence of resveratrol, with an EC50 (Half maximal effective concentration) of 44.26 mu M. This mechanism may occur through interaction with the M protein responsible for the budding of mature viral particles. Biophysical assays enabled us to characterize the interaction of the M/resveratrol complex as an entropically driven bond, guided by hydrophobic interactions at the dimerization interface of the M protein, which is essential for the stabilization and formation of the oligomers necessary for viral budding. These findings suggest that one of the targets for resveratrol binding is the M protein, indicating a potential site for blocking the progression of the infection. (AU)

• FAPESP's process: 23/09642-7 - Characterization of conformational changes in the globular domain of the M2-1 protein of hRSV and hMPV: mechanisms involving open-closed equilibrium and implications.
• Grantee: Raphael Vinicius Rodrigues Dias
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors
• FAPESP's process: 22/13050-5 - Fragment screening and rational design of mimetic peptides to search for antiviral candidates at the M2-1/phosphoprotein interaction site of human Respiratory Syncytial Virus
• Grantee: Ícaro Putinhon Caruso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/14349-1 - Evaluation of the potential effects of Kaempferol and chalcones derivatives over the RSV replication cycle in cell culture: investigating proteic mediators and metabolites in the viral cycle
• Grantee: Fátima Pereira de Souza
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/04646-9 - Interaction study between polyphenolic compounds and Human Respiratory Syncytial Virus M protein: search of binding sites for protein-protein oligomerization prevent.
• Grantee: Marcelo Andrés Fossey
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/53989-4 - Acquisition of a nuclear magnetic resonance spectrometer for studies of biomolecules
• Grantee: Raghuvir Krishnaswamy Arni
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 23/01632-2 - Characterization of conformational changes in the globular domain of the M2-1 protein of hRSV and hMPV: mechanisms involving open-closed equilibrium and implications
• Grantee: Ícaro Putinhon Caruso
• Support Opportunities: Regular Research Grants