Publications

Profile of Resistance of Human Immunodeficiency Virus to Mannose-Specific Plant Lectins

The mannose-specific plant lectins from the Amaryllidaceae family (e.g., Hippeastrum sp. hybrid and Galanthus nivalis) inhibit human immunodeficiency virus (HIV) infection of human lymphocytic cells in the higher nanogram per milliliter range and suppress syncytium formation between persistently HIV type 1 (HIV-1)-infected cells and uninfected CD4(+) T cells. These lectins inhibit virus entry. When exposed to escalating concentrations of G. nivalis and Hippeastrum sp. hybrid agglutinin, a variety of HIV-1(III(B)) strains were isolated after 20 to 40 subcultivations which showed a decreased sensitivity to the plant lectins. Several amino acid changes in the envelope glycoprotein gp120, but not in gp41, of the mutant virus isolates were observed. The vast majority of the amino acid changes occurred at the N glycosylation sites and at the S or T residues that are part of the N glycosylation motif. The degree of resistance to the plant lectins was invariably correlated with an increasing number of mutated glycosylation sites in gp120. The nature of these mutations was entirely different from that of mutations that are known to appear in HIV-1 gp120 under the pressure of other viral entry inhibitors such as dextran sulfate, bicyclams (i.e., AMD3100), and chicoric acid, which also explains the lack of cross-resistance of plant lectin-resistant viruses to any other HIV inhibitor including T-20 and the blue-green algae (cyanobacteria)-derived mannose-specific cyanovirin. The plant lectins represent a well-defined class of anti-HIV (microbicidal) drugs with a novel HIV drug resistance profile different from those of other existing anti-HIV drugs.

Polyanion Inhibitors of Human Immunodeficiency Virus and Other Viruses. 5. Telomerized Anionic Surfactants Derived from Amino Acids

omega-Acryloyl anionic surfactants, whose polar heads are derived from amino acids, have been telomerized to prepare polyanions of a predetermined molecular weight. The main goal of this study was to verify whether the antiviral activity is influenced by the degree of polymerization of the polyanions. The oligomeric polyanions were evaluated for their activity against human immunodeficiency virus (HIV-1 or HIV-2) and various other RNA and DNA viruses. With regard to their anti-HIV activity, a minimum number of anionic groups was necessary to achieve an inhibitory effect. Moreover, to be active the overall conformation of the polyanion must be such that the anionic groups are located on the external site of the molecule. With some of the polyanions, a 50% inhibition concentration (IC50) as low as 1 microgram/ mL, or even 0.1 microgram/mL, was noted against HIV-1 in CEM-4 and MT-4 cells, respectively. The most potent polyanions also proved active against human cytomegalovirus and herpex simplex virus at concentrations of 5-10 and 20-40 micrograms/mL, respectively. No activity was observed against any of the other viruses tested (i.e., vesicular stomatitis, Sindbis, Semliki forest, parainfluenza, Junin, Tacaribe, Coxsackie, polio, reo, and vaccinia). No toxicity for the host cells was observed at concentrations up to 200 micrograms/mL.

Mechanism of action of acyclic nucleoside phosphonates against herpes virus replication

Efficacy of E-5-(2-Bromovinyl)-2′-Deoxyuridine in the Topical Treatment of Herpetic Keratitis in Rabbits and Man

Topical BVDU [(E)-5-(2-bromovinyl)-2′-deoxyuridine] application (i.e. 0.1% BVDU eye drops) has proven to be highly efficacious in the treatment of both epithelial and stromal herpes simplex keratitis, both in rabbits and humans.

Coreceptor Choice and T Cell Depletion by R5, X4, and R5X4 HIV-1 Variants in CCR5-Deficient (CCR5Δ32) and Normal Human Lymphoid Tissue

Reverse engineering modelling of free-form surfaces from point clouds subject to boundary conditions

In product design, a CAD model often needs to be constructed from a physical part. This process is called reverse engineering and is performed through dimensional digitising and CAD modelling. The dimensional digitising results in a cloud of points, which are input for the CAD modelling of surfaces corresponding to the object's features. Consistent with these features, some of the modelled surfaces need to join with positional, tangential or curvature continuity. This paper reports on the incorporation of these geometric boundary conditions in the CAD modelling of free-form surfaces from a cloud of points with non-uniform rational B-splines (NURBS). The described methods are illustrated with some practical, industrial examples and some alternative solutions are briefly described.

Prospects of anti-HIV therapy and prophylaxis

Comparison between oil and water dielectric in wire EDM of tool steel

No abstract is provided for this article.

Assessment of a three-year experience with a Belgian Primary Care data Network.

The paper describes the experiences with a Belgian Primary Care data Network from 1999 till 2002. Three cycles of data collection have been performed. The network involves about 300 general practitioners (GPs) and up to 8 different software packages. This network is semi-anonymous, semi-automatic and mixed (paper and electronic with various software's). For the coming next years, efforts should be focused on solving some frequently occurring problems with the data collection through the EPR, such as a considerable number of data lacking and the fact that GPs do not always use the problem oriented structure of the EPR (Electronic Patient Record). Afterwards, more promising usage could be considered and developed such as repeated data collection using a same GPs' sample, long-term recording studies, usage of larger GPs' samples, etc.

Synthesis and Biological Evaluation of Novel 1′‐Branched and Spironucleosides Analogues.

Abstract For Abstract see ChemInform Abstract in Full Text.

Lack of retinal toxicity of the anti-CMV drug (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC)

Synthesis And Antimicrobial Activity Of Some Novel 6-Bromo-2-Methyl/phenyl-3-(Sulphonamido) quinazolin-4(3H)- Ones

A series of novel 2-substituted-3-(sulphonamido) quinazolin-4(3H)-ones have been synthesized by condensing the primary amino group of sulphamoxole and sulphadimidine with 2-substituted benzoxazin-2-one. The compounds synthesized were screened for antibacterial activity (Escherichia coil and Staphylococcus aureus) antiviral activity (Herpes simplex virus type 1 and 2 in E 6 SM cells, HIV-1 and 2 in MT-4 cells), all the test compounds exhibited comparable antibacterial activity with that of standards sulphamoxole and sulphadimidine.

CXCR4-activated astrocyte glutamate release via TNFα: amplification by microglia triggers neurotoxicity

CCDC 186098: Experimental Crystal Structure Determination

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.

The enhancement of micromachining ability of selective laser melting by selective laser erosion

Novel Bicyclic Furanopyrimidines with Dual anti‐VZV and ‐HCMV Activity.

Abstract For Abstract see ChemInform Abstract in Full Text.

Human Immunodeficiency Virus Glycoprotein gp120 as the Primary Target for the Antiviral Action of AR177 (Zintevir)

Preface