Institute of Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
MOA Key Laboratory of Animal Virology, Institute of Preventive Veterinary Sciences and Department of Veterinary Medicine, Zhejiang University, Hangzhou 310058, China.
Viruses. 2020 Feb 4;12(2):176. doi: 10.3390/v12020176.
The green tea catechin epigallocatechin gallate (EGCG) exhibits antiviral activity against various viruses. Whether EGCG also inhibits the infectivity of circovirus remains unclear. In this study, we demonstrated the antiviral effect of EGCG on porcine circovirus type 2 (PCV2). EGCG targets PCV2 virions directly and blocks the attachment of virions to host cells. The microscale thermophoresis assay showed EGCG could interact with PCV2 capsid protein in vitro with considerable affinity (Kd = 98.03 ± 4.76 μM), thereby interfering with the binding of the capsid to the cell surface receptor heparan sulfate. The molecular docking analysis of capsid-EGCG interaction identified the key amino acids which formed the binding pocket accommodating EGCG. Amino acids ARG51, ASP70, ARG73 and ASP78 of capsid were found to be critical for maintaining the binding, and the arginine residues were also essential for the electrostatic interaction with heparan sulfate. The rescued mutant viruses also confirm the importance of the key amino acids of the capsid to the antiviral effect of EGCG. Our findings suggest that catechins could act as anti-infective agents against circovirus invasion, as well as provide the basic information for the development and synthesis of structure-based anti-circovirus drugs.
绿茶儿茶素表没食子儿茶素没食子酸酯(EGCG)对多种病毒表现出抗病毒活性。然而,EGCG 是否抑制圆环病毒的感染性尚不清楚。在本研究中,我们证实了 EGCG 对猪圆环病毒 2 型(PCV2)的抗病毒作用。EGCG 直接靶向 PCV2 病毒粒子,并阻止病毒粒子附着到宿主细胞上。微量热泳动分析显示,EGCG 可以在体外与 PCV2 衣壳蛋白以相当高的亲和力相互作用(Kd = 98.03 ± 4.76 μM),从而干扰衣壳与细胞表面受体肝素硫酸的结合。衣壳-EGCG 相互作用的分子对接分析确定了形成容纳 EGCG 的结合口袋的关键氨基酸。衣壳中的氨基酸 ARG51、ASP70、ARG73 和 ASP78 对于维持结合至关重要,并且精氨酸残基对于与肝素硫酸的静电相互作用也是必需的。拯救的突变病毒也证实了衣壳关键氨基酸对 EGCG 抗病毒作用的重要性。我们的研究结果表明,儿茶素类可以作为抗圆环病毒入侵的抗感染剂,为基于结构的抗圆环病毒药物的开发和合成提供了基础信息。