Viral uptake inhibitors

Castanosp ermine has been shown to have in vitro antiviral activity against human immunodeficiency virus (HIV) [99] and human cytomegalovirus (CMV) [100], which is an opportunistic pathogen in AIDS. Alterations in viral coat glycoproteins in the presence of castanospermine are associated with a loss of infectivity. 6-0-acyl derivatives of castanospermine are more potent inhibitors of HIV growth than the natural product with the 6-O-butyryl-derivative (MDL 28,374) currently in clinical trials for AIDS. The lipophilic nature of the acyl derivative improves uptake by cells but the compound appears to be intracellularly converted to castanospermine [101]. 

The feature common to the cytotoxic effects brought on by nonreplicating influenza virus, poxvirus, and defective-interfering vesicular stomatitis virus is the high multiplicity of infection required. This has led to the assumption that the toxic effect is caused by one or more components of the parental input virion, most likely protein in origin. However, Cordell-Stewart and Taylor (1971, 1973) have provided evidence that the double-stranded viral RNA isolated from cells infected with bovine enterovirus causes a rapid cytopathic effect as determined by trypan-blue uptake or Cr release from affected Ehrlich ascites tumor cells or L1210 cells toxic effects are reduced or do not occur in cells exposed to single-stranded or heat-denatured double-stranded viral RNA and the toxic effect of bovine enteroviral double-stranded RNA is not abolished by inhibitors of protein synthesis such as puromycin or cycloheximide. 

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