In vitro and in vivo activity of AS101 against West Nile virus (WNV)

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• 作者：V. Indenbaum^a ; ^b ; H. Bin^a ; D. Makarovsky^b ; M. Weil^a ; ^b ; L.M. Shulman^a ; M. Albeck^c ; B. Sredni^b ; ¹ ; ^{srednib@mail.biu.ac.il} ; E. Mendelson^a ; ^b ; ¹ ; ^{ellamen@sheba.health.gov.il}
• 关键词：AS101 ; ammonium trichloro(dioxyethylene-0-0&prime ; )tellurate ; IVIG ; intravenous immunoglobulin ; IP ; intraperitoneal ; CPE ; cytopathic effect ; WNV-ENV or E-protein ; WNV-envelope protein ; WB ; Western blot ; PFU ; plaque forming unit
• 刊名：Virus Research
• 出版年：2012
• 期刊代码：92_01681702
• 类别：imm
• 出版时间：June, 2012
• 卷：166
• 期：1-2
• 页码：68-76
• 文件大小：827 K

摘要

There are currently no effective drugs to treat serious complications caused by WNV infection. The inhibition of WNV by the pluripotent immunomodulator AS101 [ammonium trichloro(dioxyethylene-0-0鈥?tellurate] was evaluated in vitro and in vivo, and its mechanism was explored. Adding AS101 to Vero cells 1 h or 5 min before infection increased cell survival from 21%to 84%and decreased plaque formation by 87%and virus yield by 2 logs. Following infection, high titer of WNV remained in the culture supernatants indicating interference with virus cell attachment. The binding of 伪_V尾₃ integrin to WNV and of Vero cells to anti-伪_V尾₃ antibody were inhibited by AS101, suggesting that AS101 may block this cellular WNV receptor. Daily treatment of mice with AS101 starting 1 day before lethal infection with WNV resulted in 48%survival. However, treatment beginning 3 days post infection resulted only in 16%survival. Similarly, a single dose of anti-WNV IVIG three days post infection resulted in 16%survival compared to 100%if IVIG was given on the same day of infection or 1 day later. However, when mice received combined treatment with AS101 and IVIG starting 3 days post infection, an additive effect of 33%survival was observed. Our study suggests that AS101 has a potential preventive and therapeutic effect against WNV infection.