Viral adhesion

As stated, DC-SIGN is a key mannoside receptor for exogenous pathogens that is used by viruses for entry into the lymph nodes. The inhibition of this process has thus been sought as an interesting strategy for blocking viral adhesion. Consequently, a series of mannosylated Boltom dendrimers was prepared (see later section) that were rather efficient in this respect. 

Reuter, J. D., et al. (1999), Inhibition of viral adhesion by sialic-acid-conjugated dendritic polymers, Bioconjug. Chem., 10, 271-278. 

A critical mechanism of action of n-3 polyunsaturated fatty acids is suspected to be a reduction in the endothelial production of IL-6 in response to naturally acquired viral infections. Increasing tissue concentrations of EPA and DH A markedly reduced the production of IL-6 from macrophages and endothelial cells in clinical trials and in cultured cells. In clinical intervention trials, dietary n-3 fatty acid supplementation suppressed the production of serum IL-6 in human subjects (13). In another set of normal subjects, IL-6 production was suppressed by 43% after supplementation with fish oil (14). IL-6 production was reduced by 54%, and clinical improvements were noted among patients with rheumatoid arthritis after supplementation with EPA and DHA (15). The role of EPA and DHA in reducing endothelial activation is complex and was reviewed recently by De Caterina et al. (16). These n-3 fatty acids may reduce naso-pharyngeal endothelial cell activation in response to viral adhesions, thereby reducing the severity of the illness and lessening the days of absence from school in the ill cohort. 

Prenylation has been implicated in the prevention of HIV infection. Statins have been used to inhibit HIV infection by interacting with Rho GTPases and suppress the intercellular adhesion required for viral entry. In another study with statins and HIV the mechanism of action was elucidated. The lypophilic statins... 

A more selective inhibition of NFkB can be achieved by transfecting cells with DNA coding for the natural inhibitor IkBo or a mutant IkB protein that lacks 36 N-terminal amino acids, and consequently becomes proteolysis resistant. In this way expression of adhesion molecules and monocyte adhesion and transmigration can be inhibited [87,88], The potentials and limitations of these latter types of therapy are however not fully understood as yet. Different transfection systems (adenoviral, retroviral, non-viral) are available for gene delivery purposes, all with their own potentials and restrictions. 

Tipranavir, a VIH-PR inhibitor, was launched for AIDS therapy (Figure 8.12). Pleconaril inhibits adhesion by binding the viral capsid. It is currently being evaluated for viral infections of the respiratory tract, in particular, for picornavims (meningitis) and rhinovirus (colds) (Figure 8.12). 

The adhesion of bacterial and viral pathogens to their animal-cell targets occurs through binding of lectins in the pathogens to... 

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