Rodrigues Thaina, Busso Jefferson de Souza, Dias Raphael Vinicius Rodrigues, Ottenio Lourenço Isabella, de Sa Jessica Maróstica, Carvalho Sidney Jurado de, Caruso Icaro Putinhon, Souza Fatima Pereira de, Fossey Marcelo Andres
Department of Physics, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (UNESP), Rua Cristóvão Colombo, 2265, São José do Rio Preto 15054-000, SP, Brazil.
Multiuser Center for Biomolecular Innovation (CMIB), São Paulo State University (UNESP), São José do Rio Preto 15054-000, SP, Brazil.
Int J Mol Sci. 2024 Nov 28;25(23):12790. doi: 10.3390/ijms252312790.
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 μM 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 μM. 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.
呼吸道合胞病毒(RSV)基质蛋白在病毒生命周期中起关键作用,对出芽至关重要,因为它能刺激病毒颗粒出现所需的最佳膜曲率。白藜芦醇是植物产生的一种多酚(3,4',5 - 三羟基反式芪),具有药理作用,包括抗炎和抗病毒活性。在本研究中,检测了白藜芦醇在HEp - 2(喉表皮样癌细胞)细胞中的感染后效应,并制备了重组M蛋白以表征这种相互作用背后的生物物理机制。白藜芦醇在48小时内的CC50(细胞毒性浓度50%)值被确定为297μM,HEp - 2细胞培养结果表明,在存在白藜芦醇的情况下病毒抑制率为42.7%,EC50(半数最大有效浓度)为44.26μM。这种机制可能是通过与负责成熟病毒颗粒出芽的M蛋白相互作用而发生的。生物物理分析使我们能够将M/白藜芦醇复合物的相互作用表征为一种由熵驱动的键,由M蛋白二聚化界面处的疏水相互作用引导,这对于病毒出芽所需的寡聚体的稳定和形成至关重要。这些发现表明白藜芦醇结合的靶点之一是M蛋白,这表明存在一个潜在的阻止感染进程的位点。