Inhibition of HIV replication by amino-sugar derivatives

AbstractThe 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, 74–77; (1987) Lancet i, 1025–1026]. They are thought to act by inhibiting α-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 α-glucosidase inhibitors and α-fucosidase inhibitors were found to be active at concentrations which were non-cytotoxic

Multilevel differential encoding with precentering for high-speed parallel link transceiver

A multilevel differential encoding scheme is proposed as a new approach for use in high-speed parallel transceiver systems. While incurring little or no increase in the number of links, the proposed encoding scheme overcomes two major problems in single-ended parallel links-reference ambiguity and power-line fluctuations. The proposed scheme transmits differentially encoded data among the pins and adjusts the driving current to be constant so as to minimize the L(di/dt) switching noise on the output driver power lines. A new precentering scheme is also applied to maximize the horizontal eye opening by centering all signals during a predefined time before the start of the next symbol transition. To verify the proposed schemes, a transceiver chip was designed and fabricated in 0.25-mu m CMOS technology. The chip, which consists of 1 parallel links with only three ground and three supply pins for the output drivers, employs a three-level differential encoding scheme to achieve a maximum data rate of 1.8 Gb/s with a bit error rate of less than 10(-12).X117sciescopu

Aminosugar derivatives as potential anti-human immunodeficiency virus agents.

Recent data suggest that aminosugar derivatives which inhibit glycoprotein processing have potential anti-human immunodeficiency virus (HIV) activity. These inhibitory effects may be due to disruption of cell fusion and subsequent cell-cell transmission of the acquired immunodeficiency syndrome (AIDS) virus. Free virus particles able to bind CD4-positive cells are still produced in the presence of these compounds with only partial reduction of infectivity. We now report a method to score in parallel both the degree of antiviral activity and the effect on cell division of aminosugar derivatives. We find that (i) the compounds 1,4-dideoxy-1,4-imino-L-arabinitol and N-(5-carboxymethyl-1-pentyl)-1,5-imino-L-fucitol partially inhibit the cytopathic effect (giant cell formation, etc.) of HIV and yield of infectious virus; (ii) the compounds N-methyldeoxynojirimycin and N-ethyldeoxynojirimycin reduce the yield of infectious HIV by an order of four and three logarithms, respectively; and (iii) one compound, N-butyldeoxynojirimycin, of the 47 compounds previously screened reduces infectious viral particles by a logarithmic order greater than five at noncytotoxic concentrations. In addition, long-term growth of infected cells in the presence of N-butyldeoxynojirimycin gradually decreases the proportion of infected cells, leading to eventual elimination of HIV from culture. This result suggests that replication is associated with cytolysis. The ability to break the cycle of replication and reinfection has important implications in the chemotherapy of AIDS