Indenbaum V.,Ministry of Health and Chaim Sheba Medical Center |
Indenbaum V.,Bar - Ilan University |
Bin H.,Ministry of Health and Chaim Sheba Medical Center |
Makarovsky D.,Bar - Ilan University |
And 7 more authors.
Virus Research | Year: 2012
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')tellurate] was evaluated in vitro and in vivo, and its mechanism was explored. Adding AS101 to Vero cells 1h or 5min 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 α Vβ 3 integrin to WNV and of Vero cells to anti-α Vβ 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. © 2012 Elsevier B.V. Source