The plant alkaloids castanospermine, dihydroxymethyldihydroxypyrrolidine and deoxynojirimycin have recently been shown to have potential anti-HIV activity [(1987) Proc. Natl. Acad. Sci. USA 84,8120-8124; (1987) Nature 330, 7477; Lancet i, 10251026]. They are thought to act by inhibiting a-glucosidase I, an enzyme involved in the processing of N-linked oligosaccharides on glycoproteins. We report here the relative efficacy of a spectrum of amino-sugar derivatives as inhibition of HIV cytopathicity. Several a-glucosidase inhibitors and a-fucosidase inhibitors were found to be active at concentrations which were non-cytotoxic.

Human cytomegalovirus infection is common in the general population but generally remains silent; the risk of disease is greatest in fetuses and the newborn and in immunocompromised subjects. In Of the 30 samples of DNA from mononuclear cells tested, 25 were positive for cytomegalovirus by the polymerase chain reaction. When the antibody data were decoded we found that all of the samples negative by the polymerase chain reaction were negative for antibody but that five of the 25 samples positive by the polymerase chain reaction were negative for antibody. Three of the five subjects positive by the polymerase chain reaction but negative for antibody were retested after six months. The total antibody test (Abbott) used initially was repeated on the new samples, and another total antibody test (Compenz, Northumbria Biologicals) and an IgG detection test (Medac) were performed; all three tests gave negative results. Serum from these three subjects was also analysed by western blotting with antigens derived from cytomegalovirus AD 169, and two of the samples were designated weakly positive. In all three subjects DNA from mononuclear cells remained positive by the polymerase chain reaction. CommentSeveral subjects considered not to be carriers of cytomegalovirus on the basis of their antibody state were found to be harbouring the virus in mononuclear cells in peripheral blood. Careful handling of the samples and rigorous controls ruled out contamina-M 1 2 3 4 5 6 7 8 9 10 HBVHHV CC BL 171 T M

Alpha-glucosidase I inhibitors have been shown to inhibit the replication of a broad range of enveloped viruses by preventing the correct folding of their envelope glycoproteins. This study assesses the potential of 6 O-butanoyl castanospermine (celgosivir) as a treatment for hepatitis C virus (HCV). In the absence of an adequate culture system for HCV, the closely related virus, bovine viral diarrhoea virus (BVDV), was used as a surrogate model. Using both a plaque assay and a cytopathic effect assay, celgosivir (IC50 16 and 47 microM respectively) was shown to be more potent than N-nonyl DNJ (105 and 74 microM), castanospermine (110 and 367 microM) and N-butyl DNJ (> 250 and 550 microM). Of the alpha-glucosidase inhibitors tested, only N-nonyl DNJ showed evidence of toxicity (CC50 > or = 120 microM). Two-way combinations of interferon-alpha, ribavirin and either celgosivir or castanospermine demonstrated that each could enhance the antiviral efficacy of the others, either additively or synergistically. The observation that the number of viral genomes released from BVDV-infected cells was inhibited by either castanospermine or celgosivir in parallel with the number of infectious units was taken as confirmation that these alpha-glucosidase I inhibitors block the production or release of flavivirus particles.

No abstract

No abstract