Human antiviral action

Interferons (IFN) are glycoproteins that, among other products, are released from virus-infected cells. In neighboring cells, interferon stimulates the production of "antiviral proteins." These inhibit the synthesis of viral proteins by (preferential) destruction of viral DNA or by suppressing its translation. Interferons are not directed against a specific virus, but have a broad spectrum of antiviral action that is, however, species-specific. Thus, interferon for use in humans must be obtained from cells of human origin, such as leukocytes (IFN-a), fibroblasts (IFN-P), or lymphocytes (IFN-y). Interferons are also used to treat certain malignancies and autoimmune disorders (e.g., IFN-a for chronic hepatitis C and hairy cell leukemia IFN-p for severe herpes virus infections and multiple sclerosis). 

Carbocyclic 2, 3 -didehydro-2, 3 -dideoxyguanosine [118353-05-2] (carbovir, CBV, 66), C H N O synthesized in 1988 (177),is apromising candidate for the chemotherapy of AIDS. CBV inhibits HIV replication and HIV-induced cytopathic effects in a variety of human T-lymphoblastoid cell lines at concentrations approximately two hundred- to four hundredfold below its cytotoxic concentrations (177). CBV is as effective as AZT and DDC in reducing the expression of viral antigen in HIV-infected CEM cells (177). The antiviral potency and selectivity of carbovir is comparable to the anti-HIV-1 potency and selectivity of 2, 3 -dideoxyadenosine (178). The exact mode of antiviral action of carbovir has not yet been elucidated, but may be the modulating effect of intracellular nucleotides on 5 -nucleotidase activity (179). 

Two soybean seeds saponins were shown to partially inhibit the HIV-induced cytopathology in infected human MT-2 lymphocytes cultures [143, 144]. However, no mechanism of antiviral action was presented. Saponin Bb (or I, 26), major constituent of group B saponins from soybean seeds completely inhibited HIV-induced cytopathic effects and virus-specific antigen expression 6 days after infection at concentration > 0.25 mg/ml [145]. 

Aucubin, at concentrations lower than 5 pg/mL significantly stimulated the proliferation of human peripheral blood mononuclear cells and enhanced the secretion of IFN-gamma [63], able to activate non-specific cytocidal activity in macrophages towards a variety of intracellular parasites and neoplastic cells, and also has a direct antiviral action. 

According to our hypothesis, the antiviral action of Mx proteins is based on their direct interaction with viral components essential for gene expression and genome replication (Haller and Kochs, 2002 Kochs and Haller, 1999a Kochs et al., 2002b). To show direct interaction of human MxA with viral structures, we analyze infected cells by immunofluorescence and coimmunoprecipitation. 

Interferons (IFNs) are an important class of broad spectrum antiviral cytokines found in higher animals, reptiles, fish, and birds. IFNs make up a large, still growing list of proteins, seven of which occur in humans. These are further divided into three classes types I, II, and III. Two important type I IFNs in human are IFNa and IFNy. There are at least 14 different alpha IFNs. These are produced by leukocytes and dendritic cells and are part of an innate immune response with antiviral action. IFNp, produced by fibroblasts and probably many other cells, is used in the treatment of multiple sclerosis. It inhibits viral replication and is the product of a single gene. Two synthetic... 

The 2 -chloro and 2 -bromo congeners of either 748 (FIAC) or 758 (FMAU) are more cytotoxic than FIAC and FMAU, suggesting that these chloro and bromo nucleosides, in contrast to the 2 -fluoro compounds, are comparatively better substrates for deoxycytidine kinase of human lymphocytes than the substrates for viral-specific thymidine kinase. The disposition of the 2 -fluoro group may also be important from the biological viewpoint. It should be noted that the structural difference between RNA and DNA is at the 2 -position. The ribo type of analog (738) of FIAC is 10 times less effective in suppression of HSV replication than is FIAC. Thus Fox, and Watanabe and coworkers concluded that the 2 - up fluorine disposition and the species of the substituent at C-5 are the two important factors influencing antiviral activity. Nevertheless, the mechanism of action of 2 -deoxy-2 -fluorocytidine (737) on certain herpes viruses, including HSV-1... 

Mecfianism of Action A biologic response modifier t hat interacts with specific cel 1 receptors found on surface of human cells. Therapeutic Effect Possesses antiviral and immunoregulatory activities. 

The replication of viral particles is intimately linked to the human cell which hosts these parasites they are intracellular organisms that rely on many of the host cell synthetic processes. Therapeutic options for viral infections are, therefore, limited. In the immunocompetent patient such therapy may be unnecessary and may even cause difficulty in establishing an accurate diagnosis. The antiviral agents may be considered in the following three categories depending upon mode of action ... 

Mechanism of Action. Although the details are unclear, imiquimod enhances the local production of interferons, tumour necrosis factor-alpha, and possibly other cytokines that produce antiviral responses. Hence, this drug does not act directly on the virus, but instead modulates the host (human) immune responses that have antiviral effects. 

Abstract The inhibitory action of polyanionic substances on virus replication was reported more than 50 years ago. Seaweeds, marine invertebrates, and higher plants represent abundant sources of novel compounds of proved antiviral activity. Natural sulfated polysaccharides (SPs) are potent in vitro inhibitors of a wide variety of enveloped viruses, such as herpes simplex virus (HSV) types 1 and 2, human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), dengue virus (DENV), respiratory syncytial virus (RSV), and influenza A virus. Several polysulfate compounds have the potential to inhibit virus replication by blocking the virion binding to the host cell. In contrast, their in vivo efficacy in animal and human systemic infections has undesirable draw-... 

Yamamoto, N., Schols, D., DeClercq, E. etal. (1992) Mechanism of anti-human immunodeficiency vims action of polyoxometalates, a class of broad-spectmm antiviral agents. Molecular Pharmacology, 42, 1109—1117. 

The spectrum of biological activity displayed by tetramic acid-containing natural products is remarkable in its diversity it includes potent antibiotic, antiviral and antiulcerative properties, cytotoxicity and mycotoxicity, the inhibition of tumors (in mice and humans) as well as fungicidal action." Other members of this class are responsible for the pigmentation of certain molds and sponges. 

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