Combination Chemotherapy Using Immune Modulators and Antiviral Drugs against Togaviruses and Bunyaviruses. Antiviral Therapy Against Banzi Virus, Semliki Forest Virus, and Richinde Virus

摘要

We have studied model arboviruses and arenaviruses to develop effective combination therapies using antiviral drugs and immunomodulators. In vivo screening of candidate compounds was undertaken since in vitro screening was not a reliable predictor of in vivo results. The compounds were examined using Pichinde', an arenavirus; Banzi, a flavivirus; and Semliki Forest, an alphavirus. Interferon (IFN), IFN inducers, neutralizing antiserum, ribavirin, interleukin-2 (IL-2), and tumor necrosis factor (TNF) had some prophylactic antiviral action in vivo. Certain combinations of these compounds (e.g., IFN plus TNF, ribavirin or IL-2, and IL-2, and IFN inducers plus neutralizing antiserum) provided greater than additive antiviral effects in vivo). An in vivo model was also developed to study late therapy by starting intervention at the time of viremia when the virus is spreading to target organs. Studies of combination chemotherapy and immunotherapy using the 'late therapy' model were undertaken.