Bertaux Claire, Daelemans Dirk, Meertens Laurent, Cormier Emmanuel G, Reinus John F, Peumans Willy J, Van Damme Els J M, Igarashi Yasuhiro, Oki Toshikazu, Schols Dominique, Dragic Tatjana, Balzarini Jan
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Virology. 2007 Sep 15;366(1):40-50. doi: 10.1016/j.virol.2007.04.008. Epub 2007 May 11.
We studied the antiviral activity of carbohydrate-binding agents (CBAs), including several plant lectins and the non-peptidic small-molecular-weight antibiotic pradimicin A (PRM-A). These agents efficiently prevented hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infection of target cells by inhibiting the viral entry. CBAs were also shown to prevent HIV and HCV capture by DC-SIGN-expressing cells. Surprisingly, infection by other enveloped viruses such as herpes simplex viruses, respiratory syncytial virus and parainfluenza-3 virus was not inhibited by these agents pointing to a high degree of specificity. Mannan reversed the antiviral activity of CBAs, confirming their association with viral envelope-associated glycans. In contrast, polyanions such as dextran sulfate-5000 and sulfated polyvinylalcohol inhibited HIV entry but were devoid of any activity against HCV infection, indicating that they act through a different mechanism. CBAs could be considered as prime drug leads for the treatment of chronic viral infections such as HCV by preventing viral entry into target cells. They may represent an attractive new option for therapy of HCV/HIV coinfections. CBAs may also have the potential to prevent HCV/HIV transmission.
我们研究了碳水化合物结合剂(CBA)的抗病毒活性,其中包括几种植物凝集素和非肽类小分子抗生素普拉地米星A(PRM-A)。这些制剂通过抑制病毒进入,有效地预防了丙型肝炎病毒(HCV)和1型人类免疫缺陷病毒(HIV-1)对靶细胞的感染。CBA还被证明可防止表达DC-SIGN的细胞捕获HIV和HCV。令人惊讶的是,这些制剂并未抑制单纯疱疹病毒、呼吸道合胞病毒和副流感3病毒等其他包膜病毒的感染,这表明其具有高度特异性。甘露聚糖可逆转CBA的抗病毒活性,证实了它们与病毒包膜相关聚糖的关联。相比之下,硫酸葡聚糖5000和硫酸化聚乙烯醇等聚阴离子可抑制HIV进入,但对HCV感染没有任何活性,这表明它们通过不同的机制起作用。通过防止病毒进入靶细胞,CBA可被视为治疗慢性病毒感染(如HCV)的主要药物先导。它们可能是治疗HCV/HIV合并感染的一个有吸引力的新选择。CBA也可能有预防HCV/HIV传播的潜力。