Publications

A travers les exemples du viaduc de Lembeek, le tunnel de Halle, les ponts metalliques de Halle, le croisement a Buizingen et plusieurs ponts sur la Senne, la synergie entre la conception des ouvrages et le maintien du trafic ferroviaire sur une ligne existante est mis en evidence. La diversite des ouvrages sur le troncon Lembeek-Bruxelles de la TGV est due principalement aux conditions de realisation de ces ouvrages. En outre le concept de la pose des voies sur une assiette stabilisee au moyen d'un revetement en hydrocarbones est presente.

The chemokine receptors CCR5 and CXCR4 function as the principal coreceptors for human immunodeficiency virus type 1 (HIV-1). Coreceptor function has also been demonstrated for a variety of related receptors in vitro. The relative contributions of CCR5, CXCR4, and other putative coreceptors to HIV-1 disease in vivo have yet to be defined. In this study, we used sequential primary isolates and recombinant strains of HIV-1 to demonstrate that CXCR4-using (X4) viruses emerging in association with disease progression are highly pathogenic in ex vivo lymphoid tissues compared to CXCR4-independent viruses. Furthermore, synthetic receptor antagonists that specifically block CXCR4-mediated entry dramatically suppressed the depletion of CD4(+) T cells by recombinant and clinically derived X4 HIV-1 isolates. Moreover, in vitro specificity for the additional coreceptors CCR3, CCR8, BOB, and Bonzo did not augment cytopathicity or diminish sensitivity toward CXCR4 antagonists in lymphoid tissues. These data provide strong evidence to support the concept that adaptation to CXCR4 specificity in vivo accelerates HIV-1 disease progression. Thus, therapeutic intervention targeting the interaction of HIV-1 gp120 with CXCR4 may be highly valuable for suppressing the pathogenic effects of late-stage viruses.

Polyhydroxycarboxylates (MW 3800–14000) derived from phenolic (PDP) compounds were found to be selective inhibitors of human cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), thymidine kinase-deficient (TK − ) HSV-1 and vaccinia virus replication at concentrations that are not toxic to the host cells. The PDP compounds were not inhibitory to parainfluenza virus, reovirus, Sindbis virus, or Semliki forest virus. The polycarboxylate aurintricarboxylic acid (ATA) (MW 1149–3336) also proved inhibitory to CMV and HSV replication. The anti-CMV and anti-HSV activities of the ATA polymers increased with increasing molecular weight. The mechanism of anti-CMV activity of both the PDP and ATA series of compounds can be attributed to the inhibition of virion attachment to the cells, probably due to an interaction of these polyanionic compounds with the positively charged domains of the viral envelope glycoproteins.

In this study, a novel series of diarylpyrimidine derivatives with Fsp³-enriched spirocycles were designed and synthesized to further explore the chemical space of the hydrophobic channel of the NNRTI-binding pocket. The biological evaluation results showed that most of the compounds displayed effective inhibitory potency against the HIV-1 wild-type strain, with EC₅₀ values ranging from micromolar to submicromolar levels. Among them, TT6 turned out to be the most effective inhibitor with an EC₅₀ value of 0.17 μM, demonstrating up to 47 times more active than that of reference drug 3TC (EC₅₀ = 8.01 μM). More encouragingly, TT6 was found to potently inhibit the HIV-1 mutant strain K103N with an EC₅₀ value of 0.69 μM, being about 6-fold more potent than 3TC (EC₅₀ = 3.68 μM) and NVP (EC₅₀ = 4.62 μM). Furthermore, TT6 exhibited the most potent inhibitory activity toward HIV-1 reverse transcriptase with an IC₅₀ value of 0.33 μM. Additionally, molecular simulation studies were conducted to investigate the binding modes between TT6 and NNRTI-binding pocket, which may provide valuable clues for the follow-up structural optimizations.

Abstract A novel, green and efficient method for the synthesis of the title pyranopyridone and pyranopyran derivatives using a one‐pot three‐component reaction is developed.