title: In vitro and in vivo activity of AS101 against West Nile virus (WNV).
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 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 α(V)β(3) integrin to WNV and of Vero cells to anti-α(V)β(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.
authors.affiliation: Central Virology Laboratory, Public Health Services, Ministry of Health and Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: V
authors.initials: V
authors.lastname: Indenbaum
authors.forename: H
authors.initials: H
authors.lastname: Bin
authors.forename: D
authors.initials: D
authors.lastname: Makarovsky
authors.forename: M
authors.initials: M
authors.lastname: Weil
authors.forename: L M
authors.initials: LM
authors.lastname: Shulman
authors.forename: M
authors.initials: M
authors.lastname: Albeck
authors.forename: B
authors.initials: B
authors.lastname: Sredni
authors.forename: E
authors.initials: E
authors.lastname: Mendelson
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D002470:Cell Survival; D002522:Chlorocebus aethiops; D005030:Ethylenes / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D011991:Receptors, Virus / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome; D014709:Vero Cells; D010948:Viral Plaque Assay; D053585:Virus Attachment / Q000187:drug effects; D014902:West Nile virus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D005030:Ethylenes; D011991:Receptors, Virus; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate