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

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 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 αVβ3 integrin to WNV and of Vero cells to anti-αVβ3 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.

► AS101 significantly inhibited WNV plaque formation and virus yield and increased Vero cell survival.
► AS101 inhibited binding of αVβ3 integrin to WNV and of anti-αVβ3 to Vero cells.
► AS101 interacts with αVβ3 integrin.
► Daily treatment with AS101 protected mice from a lethal dose of WNV by 48%.