Neurath A R, Strick N, Li Y Y
Lindsley F Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA.
Antivir Chem Chemother. 1998 Mar;9(2):177-84. doi: 10.1177/095632029800900209.
The spread of sexually transmitted diseases, including human immunodeficiency virus type 1 (HIV-1) and herpesvirus infections, has continued unabated despite educational efforts spearheaded as a response to the HIV-1 epidemic. This suggests the need for prophylactic measures, including the application of topical antiviral agents. Chemical modification of bovine beta-lactoglobulin (beta-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the generation of a potent HIV-1 inhibitor (designated 3HP-beta-LG) shown to also have activity against herpes simplex virus types 1 and 2 (HSV-1, HSV-2). This report provides more detailed results concerning the anti-herpesvirus activity of 3HP-beta-LG, indicating that this compound: (i) inhibited infection by human cytomegalovirus (HCMV), which is known to be sexually transmitted; (ii) inactivated the infectivity of both HSV-1 and HSV-2; (iii) inhibited cell-to-cell transmission of HSV-1 and HSV-2; and (iv) bound to HSV-1, HSV-2 and HCMV virus particles and partially inhibited the binding of anti-glycoprotein E (gE) and anti-gC monoclonal antibodies to HSV-1 and HSV-2. The binding of 3HP-beta-LG to the herpesviruses under study was inhibited by aggregated human IgG, suggesting that the respective viral Fc receptor is one of the target sites for 3HP-beta-LG. In agreement with results on inhibition of HIV-1 infection, 3HP-beta-LG appears to be the acid anhydride-modified protein of choice as an antiviral agent against herpesviruses.
尽管针对人类免疫缺陷病毒1型（HIV-1）疫情开展了教育宣传活动，但包括HIV-1和疱疹病毒感染在内的性传播疾病仍在持续蔓延。这表明需要采取预防措施，包括应用局部抗病毒药物。用羟基邻苯二甲酸酐（3HP）对乳清中的主要蛋白质牛β-乳球蛋白（β-LG）进行化学修饰，产生了一种有效的HIV-1抑制剂（命名为3HP-β-LG），该抑制剂还显示出对1型和2型单纯疱疹病毒（HSV-1、HSV-2）有活性。本报告提供了关于3HP-β-LG抗疱疹病毒活性的更详细结果，表明该化合物：（i）抑制已知可通过性传播的人巨细胞病毒（HCMV）感染；（ii）使HSV-1和HSV-2的感染性失活；（iii）抑制HSV-1和HSV-2的细胞间传播；（iv）与HSV-1、HSV-2和HCMV病毒颗粒结合，并部分抑制抗糖蛋白E（gE）和抗gC单克隆抗体与HSV-1和HSV-2的结合。聚集的人IgG可抑制3HP-β-LG与所研究疱疹病毒的结合，这表明相应的病毒Fc受体是3HP-β-LG的靶位点之一。与抑制HIV-1感染的结果一致，3HP-β-LG似乎是作为抗疱疹病毒的抗病毒剂的首选酸酐修饰蛋白。
