Screening of Immunoenhancing Drugs with Antiviral Activity against Members of the Arena-, Alpha-, and Adenoviridae.

摘要

Twenty-eight compounds or combinations of compounds were screened for their in vivo antiviral activity. Several preparations were found to be able to protect mice from challenge with mouse adenovirus but not Venezuelan equine encephalitis (VEE) virus. Only two compounds (AVS-1762 and AVS-1968) had any effect on survival of mice infected with VEE. Additionally, AVS-1758 was able to reduce the level of circulating VEE but was not able to alter the outcome of the infection. Macrophage activation for cytolysis of virally infected targets was found to be different from cytolysis of a standard tumor target in sensitivity to stimuli, kinetics of the response, and sensitivity to inhibitors. This indicated that detection of changes in effector functions in nonviral systems may not be applicable to viral systems. The ability of various potential immunomodulators to effect macrophage, natural killer cell, and cytotoxic T-cell responses were measured using virally infected cells as targets. Finally attempts were made to develop a mouse-lethal strain of Pichinde virus. Two plaque-type variant that grew well on mouse L-929 cells were isolated. However, neither produced disease in adult mice. (jes)