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

V. Indenbaum, H. Bin, D. Makarovsky, M. Weil, L. M. Shulman, M. Albeck, B. Sredni, E. Mendelson

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)68-76
Number of pages9
JournalVirus Research
Volume166
Issue number1-2
DOIs
StatePublished - Jun 2012

Bibliographical note

Funding Information:
This work was supported by funds provided by the Israel Ministry of Health , The Safdié Institute for AIDS and Immunology Research , The Comet-Walerstein Cancer Research Program , The Dave and Florence Muskovitz Chair in Cancer Research and the Frieda Stollman Cancer Memorial Fund .

Funding

This work was supported by funds provided by the Israel Ministry of Health , The Safdié Institute for AIDS and Immunology Research , The Comet-Walerstein Cancer Research Program , The Dave and Florence Muskovitz Chair in Cancer Research and the Frieda Stollman Cancer Memorial Fund .

FundersFunder number
Frieda Stollman Cancer Memorial Fund
Israel Ministry of Health
Safdié Institute for AIDS and Immunology Research

    Keywords

    • AS101
    • Virus inhibition
    • WNV
    • West Nile virus
    • α β integrin

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