Publications

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CXCL12(AF647) is a valuable, more convenient alternative for [(125)I]CXCL12 in ligand/receptor interaction studies.

Synthesis of 9-(2,3-dideoxy-3-fluoro-beta-D-ribofuranosyl)-2-chloroadenine (7b) and -2-chloro-6-methoxypurine (9b), as well as the alpha-D-anomer 7a of the former and its N-7 isomer 10a is reported. Among the compounds synthesized, only the beta-D-anomer 7b displays moderate cytotoxic activity.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

A new polyacetal polysulphate, termed PAPS, was synthesized starting from dextran through oxidation, reduction, and subsequent sulphation. PAPS inhibited HIV-1- and HIV-2-induced cytopathicity in MT-4 cells at concentrations comparable to those required for dextran sulphate (MW5000) to inhibit the cytopathicity of these viruses (50% inhibitory concentration: 0.4–0.04 μg ml −1 ). At these concentrations PAPS had no anticoagulant activity. PAPS suppressed syncytium formation between MOLT-4 cells and persistently HIV-1- or HIV-2-infected HUT-78 cells at a concentration of 1 μg ml −1 , that is 25- to 30-fold lower than that required for dextran sulphate to inhibit syncytium formation. Like dextran sulphate, PAPS inhibited HIV-1 binding to the cells and anti-gp120 mAb binding to HIV-1 gp120. Also, PAPS proved equally active as dextran sulphate against herpes simplex virus, cytomegalovirus and the arenaviruses Junin and Tacaribe, and 10-fold more active than dextran sulphate against vaccinia, Sindbis, influenza A, and vesicular stomatitis virus. Neither PAPS nor dextran sulphate proved inhibitory to the non-enveloped viruses polio, Coxsackie and reovirus. Pharmacokinetic studies in rabbits revealed that after intravenous bolus injection the serum concentrations of PAPS decayed biphasically, with an initial half-life of approximately 45–60 min. Twenty-four hours following their intraperitoneal administration to mice, PAPS as well as dextran sulphate generated low titres of an antiviral principle that was at least partially interferon-like.

No abstract is provided for this article.

The new compounds guttiferone O ( 1) and 3-methoxycheffouxanthone ( 2) have been isolated from the seeds of Garcinia afzelii Engl., together with nine known compounds: 2-hydroxy-1,7-dimethoxyxanthone ( 3), smeathxanthone A ( 4), 1,5-dihydroxyxanthone ( 5), 1,6-dihydroxy-5-methoxyxanthone ( 6), cheffouxanthone ( 7), 1,3,5-trihydroxyxanthone ( 8), smeathxanthone B ( 9), isoxanthochymol ( 10) and guttiferone E ( 11). Their structures were elucidated by means of 1D and 2D-NMR techniques. All the isolates showed high cytotoxic activity and were found inactive when tested against HIV and influenza viruses.

We have established a convenient animal model for flavivirus encephalitis using Montana Myotis leukoencephalitis virus (MMLV), a bat flavivirus. This virus has the same genomic organization, and contains the same conserved motifs in genes that encode potential antiviral targets, as flaviviruses that cause disease in man (N. Charlier et al., accompanying paper), and has a similar particle size (approximately 40 nm). MMLV replicates well in Vero cells and appears to be equally as sensitive as yellow fever virus and dengue fever virus to a selection of experimental antiviral agents. Cells infected with MMLV show dilation of the endoplasmic reticulum, a characteristic of flavivirus infection. Intraperitoneal, intranasal or direct intracerebral inoculation of SCID mice with MMLV resulted in encephalitis ultimately leading to death, whereas immunocompetent mice were refractory to either intranasal or intraperitoneal infection with MMLV. Viral RNA and/or antigens were detected in the brain and serum of MMLV-infected SCID mice, but not in any other organ examined: MMLV was detected in the olfactory lobes, the cerebral cortex, the limbic structures, the midbrain, cerebellum and medulla oblongata. Infection was confined to neurons. Treatment with the interferon-alpha/beta inducer poly(I).poly(C) protected SCID mice against MMLV-induced morbidity and mortality, and this protection correlated with a reduction in infectious virus titre and viral RNA load. This validates the MMLV model for use in antiviral drug studies. The MMLV SCID model may, therefore, be attractive for the study of chemoprophylactic or chemotherapeutic strategies against flavivirus infections causing encephalitis.

Bicyclic furanopyrimidine nucleoside analogues (BCNAs) have been previously reported as potent and selective anti-varicella-zoster virus (VZV) agents. Few modifications on the sugar moiety have been considered so far but some of them have shown interesting activity against human cytomegalovirus (HCMV) while losing activity against VZV. In addition, recent work has led to an entirely new series of anti-HCMV bicyclic furopyrimidine agents, acting through a non-nucleoside mechanism. In order to further investigate structure-activity relationship studies on the sugar moiety, some 3'- and 5'-chloro derivatives and 5'-deoxygenated derivatives have been synthesized. The lack of anti-VZV activity of the 5'-modified derivatives is further proof of a mechanism of action involving VZV thymidine kinase (TK)-mediated phosphorylation. Similarly, the replacement of the 3'-OH with chlorine showed a decrease of antiviral activity, which can be correlated to the lack of interaction with VZV TK as demonstrated by enzyme assays. These results confirm free 5'-OH and 3'-OH as necessary requirements for efficient recognition by VZV TK and for potent anti-VZV activity in cell culture.