van der Meer F J U M, de Haan C A M, Schuurman N M P, Haijema B J, Peumans W J, Van Damme E J M, Delputte P L, Balzarini J, Egberink H F
Department of Immunology and Infectious Diseases, Division of Virology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
Antiviral Res. 2007 Oct;76(1):21-9. doi: 10.1016/j.antiviral.2007.04.003. Epub 2007 May 21.
Coronaviruses are important human and animal pathogens, the relevance of which increased due to the emergence of new human coronaviruses like SARS-CoV, HKU1 and NL63. Together with toroviruses, arteriviruses, and roniviruses the coronaviruses belong to the order Nidovirales. So far antivirals are hardly available to combat infections with viruses of this order. Therefore, various antiviral strategies to counter nidoviral infections are under evaluation. Lectins, which bind to N-linked oligosaccharide elements of enveloped viruses, can be considered as a conceptionally new class of virus inhibitors. These agents were recently evaluated for their antiviral activity towards a variety of enveloped viruses and were shown in most cases to inhibit virus infection at low concentrations. However, limited knowledge is available for their efficacy towards nidoviruses. In this article the application of the plant lectins Hippeastrum hybrid agglutinin (HHA), Galanthus nivalis agglutinin (GNA), Cymbidium sp. agglutinin (CA) and Urtica dioica agglutinin (UDA) as well as non-plant derived pradimicin-A (PRM-A) and cyanovirin-N (CV-N) as potential antiviral agents was evaluated. Three antiviral tests were compared based on different evaluation principles: cell viability (MTT-based colorimetric assay), number of infected cells (immunoperoxidase assay) and amount of viral protein expression (luciferase-based assay). The presence of carbohydrate-binding agents strongly inhibited coronaviruses (transmissible gastroenteritis virus, infectious bronchitis virus, feline coronaviruses serotypes I and II, mouse hepatitis virus), arteriviruses (equine arteritis virus and porcine respiratory and reproductive syndrome virus) and torovirus (equine Berne virus). Remarkably, serotype II feline coronaviruses and arteriviruses were not inhibited by PRM-A, in contrast to the other viruses tested.
冠状病毒是重要的人类和动物病原体,由于新型人类冠状病毒如SARS-CoV、HKU1和NL63的出现,其相关性有所增加。冠状病毒与环曲病毒、动脉炎病毒和罗氏病毒一起属于尼多病毒目。到目前为止,几乎没有抗病毒药物可用于对抗该目病毒的感染。因此,各种对抗尼多病毒感染的抗病毒策略正在评估中。凝集素可与包膜病毒的N-连接寡糖元件结合,可被视为一类概念上全新的病毒抑制剂。最近对这些药物针对多种包膜病毒的抗病毒活性进行了评估,结果表明在大多数情况下,它们能在低浓度下抑制病毒感染。然而,关于它们对尼多病毒的疗效的知识有限。在本文中,评估了植物凝集素朱顶红杂合凝集素(HHA)、雪花莲凝集素(GNA)、大花蕙兰凝集素(CA)和异株荨麻凝集素(UDA)以及非植物来源的普拉地米星-A(PRM-A)和氰胍蛋白-N(CV-N)作为潜在抗病毒药物的应用。基于不同的评估原则比较了三种抗病毒试验:细胞活力(基于MTT的比色测定)、感染细胞数量(免疫过氧化物酶测定)和病毒蛋白表达量(基于荧光素酶的测定)。碳水化合物结合剂的存在强烈抑制了冠状病毒(传染性胃肠炎病毒、传染性支气管炎病毒、猫冠状病毒血清型I和II、小鼠肝炎病毒)、动脉炎病毒(马动脉炎病毒和猪繁殖与呼吸综合征病毒)和环曲病毒(马伯尔尼病毒)。值得注意的是,与其他测试病毒相比,PRM-A对猫冠状病毒血清型II和动脉炎病毒没有抑制作用。