Lusvarghi Sabrina, Bewley Carole A
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Viruses. 2016 Oct 24;8(10):296. doi: 10.3390/v8100296.
Griffithsin (GRFT), an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. It is currently being developed as a microbicide with broad-spectrum activity against several enveloped viruses. GRFT can inhibit human immunodeficiency virus (HIV) infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. The potential to inhibit other viruses as well as parasites has also been demonstrated. Griffithsin's antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. Here, we review structural and biochemical studies that established mode of action and facilitated construction of GRFT analogs, mechanisms that may lead to resistance, and in vitro and pre-clinical results that support the therapeutic potential of this lectin.
格里菲斯素(GRFT)是一种源自藻类的凝集素,是迄今为止发现的最有效的病毒进入抑制剂之一。它目前正在被开发成一种对多种包膜病毒具有广谱活性的杀菌剂。GRFT在皮摩尔浓度下就能抑制人类免疫缺陷病毒(HIV)感染,超过了大多数抗HIV药物的能力。它抑制其他病毒以及寄生虫的潜力也已得到证实。格里菲斯素的抗病毒活性源于其与高甘露糖寡糖中存在的末端甘露糖结合并交联病毒包膜糖蛋白表面这些聚糖的能力。在此,我们综述了确定其作用方式并促进GRFT类似物构建的结构和生化研究、可能导致耐药性的机制以及支持这种凝集素治疗潜力的体外和临床前研究结果。