Inhibition of antiviral activity

Since the ceramide portions of more and less inhibitory glycoliplds are very similar, differential Inhibition of antiviral activity of mouse fibroblast interferon must be related to their carbohydrate side chains. We therefore assayed antiviral activity in the presence of various saccharides contained in gangiiosides. As seen in Figure 3, both N-acetylneuraminyl lactose and N-acetyl-neuraminic acid inhibited antiviral activity, requiring approximately equal concentrations to obtain complete inhibition (60 mM). However, in comparison to GM3, 600-fold higher concentrations of these sugars had to be employed to yield complete inhibition of antiviral activity. N-glycolyineuraminic acid and the 6-methyi-... 

Replacement of the sulfur atom in the thiosemicarba2one moiety by an oxygen atom leads to a loss of antiviral activity. Methisa2one has no significant effect on vaccinia vims DNA synthesis (14) but seems to inhibit late protein synthesis by a mechanism that remains to be elucidated. 

Amino-5-iodo-2, 5 -dideoxyuridine [56045-73-9] (13) C2H22IN2O4, was synthesized ia 1975 (27) and was found effective against herpes keratitis ia rabbits (28). This compound is markedly less cytotoxic than IdU, iadicating that it may have a safer and more specific mode of antiviral activity. A potential limitation of this group of nucleosides is their specificity, for they fail to inhibit all strains of herpes vimses. The specific antiviral activity of (13) is considered to be a result of the incorporation of the 5 -Ai-phosphate into both viral and host DNA in infected cells, but not into the DNA of normal cells. Phosphorylation of (13) occurs only in herpes vims-infected cells, brought about by a vims-induced thymidine kinase (29). 

Despite very good inhibitory potency on the enzyme level, AG1284 has rather modest antiviral activity in vitro (Table 6). The reason for this discrepancy is unclear but could be related to the low water solubility and higher affinity for membranes, which may effect cell partitioning. A similar lack of correlation between the potency of enzyme inhibition and antiviral activity has been previously observed with other HIV PR inhibitors [11]. 

Scheme 7 Microwave methods for preparation of C2-symmetric HIV-1 protease inhibitors modified in Pl/Pl, enzyme inhibition, and antiviral activity in cell culture...

The synthetic triazole nucleoside, ribavirin (1-beta-D-ribofuranosyl-l,2,4-triazole-3-carboxamide, tribavirin, virazole), has a broad spectrum of antiviral activity, including DNA as well as RNA viruses (1). Ribavirin closely resembles guanosine and is converted intracellu-larly to mono-, di-, and triphosphate derivatives, which inhibit the virally induced enzymes involved in viral nucleic acid synthesis by different mechanisms that are not fully understood (2). Of the DNA viruses, ribavirin is active against Herpes simplex virus and hepatitis B virus among the RNA viruses, good activity has been observed against hepatitis C virus, orthomyxoviruses. 

A mechanism of antiviral activity of sea cucumber triterpene glycosides may be connected with antiviral protection at the stage of virus-cell interaction. This type of protection was confirmed by experiments on inhibition of the cytopathic effect of vesicular stomatite, poliomyelitis and other viruses in cell culture by cucumariosides [104]. Cucumarioside A2-2 (18) was shown to be... 

Reports of antiviral activity have been mainly confined to (XXV), R = p -Cl and R = p-OMe). The compounds were active in vitro only when pre-incubated with virus and have no effect on the replicative cycle of influenza, parainfluenza, measles, herpes and Newcastle disease viruses. There was however, some inhibition of growth of ECHO, rhinovirus, rubella and respiratory syncytial virus when the compounds were added... 

Glycosylation of interferon, produced by mouse L cells after induction by Newcastle disease virus, has been inhibited by tunicamycin with no loss of antiviral activity. 

M. D, Rose, et al. [110] discussed the inhibition and antiviral activity consequence S3mthesis of 14- and 15-membered macrocycles for HIV-1 protease inhibitors (Pis) as obtained by ringclosing metathesis of the respective linear Pis. The macrocycles were very highly active than the linear precursors and compound 143, with a 2-thiazolyl ring was the best potent PI of this... 

IL-8 also acts on nonleukocytic cells such as melanoma cells and synovial fibroblasts (16) in vitro. IL-8 enhances viral replication, particularly cytomegalovirus, in human fibroblasts in vitro (7 7). IL-8 significantly inhibits the antiviral activities of interferon-a (18). IL-8 also increases the adhesion to unstimulated human umbilical cord vein endothelial cells (HU VECs) (19), enhances transendothelial migration (20), and induces angiogenesis in rat cornea (21). 

Wilkerson et al. [76] also synthesized and evaluated a series of unsym-metrical benzamide derivatives (19). They reported several QSAR models. QSAR 10 and 11 represents their best models for enzyme inhibition and antiviral activity. 

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