Tragacanthin polysaccharides from Astragalus brachycentrus (AV208) and
Astragalus echidnaeformis (AV212) plants, which are devoid of in vitr
o antiviral activity, were evaluated in a mouse model of Punta Toro vi
rus (PTV) infection. The PTV (a phlebovirus member of the Bunyaviridae
family of viruses) is a model for studying the treatment of Rift Vall
ey fever and hantavirus infections. Single intraperitoneal treatments
with 12.5-200 mg/kg/day doses of AV212 given 24 h before or 4 and 24 h
after virus inoculation protected the majority of mice from mortality
. Single treatments with AV208 were ineffective when given 24 h before
the virus challenge; however, protection was afforded when treatments
were administered at 4 and 24 h following virus inoculation. In a fol
low-up study, AV208 treatments of 1.6-50 mg/kg/day given 24 h subseque
nt to virus exposure caused reductions in mortality, liver infection s
cores, liver and spleen virus titers, and serum transaminases, The pol
ysaccharides did not activate lymphocytes or natural killer cells, nor
was interferon induced in treated mice. However, mice pretreated with
fumed silica (a macrophage poison) and infected with the PTV were not
protected by subsequent administration of AV208 or AV212 at 50 mg/kg,
providing evidence that activation of peritoneal macrophages by the p
olysaccharides affords protection to infected animals. These compounds
should be considered for the potential treatment of significant human
infections induced by bunyaviruses and hantaviruses.