Combination Chemotherapy Using Immune Modulators and Antiviral Drug against Togaviruses and Bunyaviruses.

摘要

We have studied model arboviruses and arenaviruses to develop effective combination therapies using antiviral drugs and immunomodulators. The compounds were examined using Pichinde' (PIC) an arenavirus; Banzi (BZ) and West Nile (WN), two flaviviruses; Semliki Forest (SF), an alphavirus; and Bunyamwera (BW) and LaCrosse (LAC), two Bunyaviruses. Ribavirin was very effective against PIC, allowing for the development of lasting immunity to reinfection in surviving animals. Interferon (IFN) and IFN inducers had a consistent prophylactic antiviral action against all arboviruses tested, while not affecting PIC infection. The combination of ribavirin and IFN-Alpha/Beta provided a synergistic antiviral effect against BZ, SF, and LAC; tumor necrosis factor (TNF) and IFN-Alpha/Beta provided greater than additive antiviral effect against BZ, while the combination of interleukin-2 with IFN-Alpha/Beta erratic results against the same viruses. Finally, successful combined therapy of SF or BZ infected mice was achieved with poly I:CLC and antibodies, when the intervention was started at the time of virus spread to the target organs. This treatment provided a strong, long lasting immunity in treated animals. Keywords: Immunomodulators; Antivirals; Arboviruses; Arenaviruses; Combination therapy; RAI. (KT)