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At least 19 recordsLinked to original sources
PubMed2006

Recent advances in antiviral agents: antiviral drug discovery for hepatitis viruses.

Hepatitis B virus (HBV)- or hepatitis C virus (HCV)- associated liver diseases are now one of the important health problems in the world because of the high numbers of patients and the serious consequences. Recently, however, relatively effective treatments with antiviral agents have become available. Interferon (IFN), lamivudine and adefovir are now approved for treatment of HBV-associated liver diseases and they have been shown to be fairly effective. The goal of treatments for HBV-associated liver disease is to achieve a clinical cure in as short a period as possible without producing resistance mutation of the virus. Several nucleotide analogues with more potent antiviral activities are now in clinical trials. In the case of HCV-associated liver diseases, Pegylated IFN (Peg IFN) + ribavirin combination therapy is the standard and most effective treatment with a sustained response of 60-70%. The goal of the treatments for these liver diseases is to induce the complete eradication of the infected virus and at present new anti HCV drugs targeting the molecular segments of the virus are under development. It is expected that the complete eradication of infected virus will be possible in most cases in the near future.

Antiviral Agents↗
PubMed1987

Polysaccharides as antiviral agents: antiviral activity of carrageenan.

A number of polysaccharides showed good antiviral activity against several animal viruses. At 5 micrograms/ml, carrageenan prevented the cell monolayer from destruction by herpes simplex virus type 1 (HSV-1) growth. At 10 micrograms/ml, carrageenan reduced the formation of new infectious HSV-1 by almost five logs. No cytotoxic effects were detected with concentrations of carrageenan up to 200 micrograms/ml. When 10 micrograms of carrageenan per ml was added at the beginning of HSV-1 infection of HeLa cells, there was potent inhibition of viral protein synthesis, and the cells continued synthesizing cellular proteins. This did not occur if carrageenan was added 1 h after HSV-1 infection. The use of [35S]methionine-labeled virions to analyze the entry of HSV-1 or Semliki Forest virions into cells indicated that carrageenan had no effect on virus attachment or virus entry. Moreover, carrageenan did not block the early permeabilization of cells to the toxic protein alpha-sarcin. These results suggest that this sulfated polysaccharide inhibits a step in virus replication subsequent to viral internalization but prior to the onset of late viral protein synthesis.

Animals↗
PubMed2006

Prevention of VZV infection in immunosuppressed patients using antiviral agents.

Antiviral agents play a key role in the prevention and treatment of varicella zoster virus (VZV) disease in immunosuppressed patients. Randomized trials show that aciclovir is effective in preventing VZV reactivation disease; however, no consensus exists on dose, duration and patient population for its use. The recent shortage of VZV-specific immunoglobulin has generated renewed interest in the use of antiviral agents as post-exposure prophylaxis. The use of antiviral agents for post-exposure prophylaxis is not supported by randomized trials, but uncontrolled experience suggests that it might be a reasonable alternative if varicella-specific immunoglobulin is not available. Current evidence on the use of antiviral agents in the prevention of reactivation disease and management of exposure to VZV is discussed.

Acyclovir↗
PubMed1992

Antiviral agents.

Antiviral agents are less numerous and often more toxic than antibacterial agents. Acyclovir is commonly used for suppression and treatment of recurrent genital herpes simplex virus and may be indicated for pregnant women with disseminated herpes. Zidovudine is indicated for pregnant women with human immunodeficiency virus infection who have low CD4 lymphocyte counts. Ganciclovir, vidarabine, ribavirin, amantadine, didanosine, and foscarnet are rarely indicated in gynecology and are not recommended for use in pregnancy.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Short, discontinuous exposure to butyrate effectively sensitizes latently EBV-infected lymphoma cells to nucleoside analogue antiviral agents.

Antiviral drugs alone have been unsuccessful in the treatment of Epstein-Barr virus (EBV)-associated malignancies because the virus maintains a latent state of replication in these tumors. In recent years, novel therapeutic approaches are being investigated wherein lytic replication of the virus is induced prior to the use of cytotoxic antiviral drugs. The choice of suitable agents to induce lytic replication has been a critical step in this novel approach. We have previously demonstrated that butyrate derivatives induce a lytic pattern of EBV gene expression in patient-derived EBV-positive lymphoblastoid cell lines and, together with nucleoside analogue ganciclovir, effectively reduce or eliminate tumor growth in humans. Butyrate has drawbacks as a therapeutic agent, however, as constant intravenous infusion is required to achieve detectable plasma levels of this drug. In this study, we investigated whether discontinuous exposure to butyrate is capable of initiating lytic phase gene expression and thymidine kinase induction, and sensitizing EBV-positive lymphoma cells to ganciclovir-mediated cell growth arrest and apoptosis. We demonstrate that multiple daily 6-h exposures of the EBV-positive Burkitt's lymphoma cell line P3HR1 to butyrate induced sustained expression of the EBV lytic phase protein BMRF. Viral thymidine kinase was also induced by intermittent exposure, although to a lower level than with continuous exposure treatment. However, discontinuous exposure to butyrate in combination with ganciclovir induced a similar level of tumor cell growth inhibition as did continuous treatment, as measured by serial enumeration of viable cells, MTT cell proliferation assays and measurement of cellular DNA content. We further demonstrated that those cells which survived initial exposure to butyrate plus ganciclovir remained susceptible to further cycles of combination treatment. These findings suggests that continuous infusion of butyrate may not be necessary for maintaining viral thymidine kinase gene expression and sensitization to antiviral agents in EBV-associated tumors, and that therapeutic regimens which employ more convenient, discontinuous exposure to butyrate may also be effective clinically.

Antiviral Agents↗
PubMed1973

Mechanism of action of 1- -D-ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole), a new broad-spectrum antiviral agent.

The antiviral activity of the synthetic nucleoside, Virazole (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), against measles virus in Vero cell cultures was substantially reversed by xanthosine, guanosine, and to a slightly lesser extent by inosine. Virazole 5'-phosphate was subsequently found to be a potent competitive inhibitor of inosine 5'-phosphate dehydrogenase (IMP:NAD(+) oxidoreductase, EC 1.2.1.14) isolated from Escherichia coli (K(m) = 1.8 x 10(-5) M) with a K(i) of 2.7 x 10(-7) M. Guanosine 5'-phosphate (GMP) was a competitive inhibitor of this enzyme with a K(i) of 7.7 x 10(-5) M. Virazole 5'-phosphate was similarly active against IMP dehydrogenase isolated from Ehrlich ascites tumor cells, with a K(i) of 2.5 x 10(-7) M. The K(m) for this enzyme was 1.8 x 10(-5) M, and the K(i) for GMP was 2.2 x 10(-4) M. These results suggest that the antiviral activity of Virazole might be due to the inhibition of GMP biosynthesis in the infected cell at the step involving the conversion of IMP to xanthosine 5'-phosphate. This inhibition would consequently result in inhibition of the synthesis of vital viral nucleic acid.

Alkaline Phosphatase↗
PubMed1989

Tubulointerstitial nephritis caused by the antiviral agent foscarnet.

The antiviral agent foscarnet has long been used in our unit to treat cytomegalovirus (CMV) infections in renal transplant patients. The clinical effect has been convincing and, apart from changes in serum calcium levels, very few side effects have been noted. We have, however, observed a nephrotoxic reaction in a series of patients with initially good renal function who therefore received high doses of foscarnet. Transplant biopsies performed in five of those patients revealed degenerative changes in the tubular epithelial cells as well as tubular calcium deposits and an infiltration of the interstitium by mixed mononuclear and polymorphonuclear leucocytes. Renal insufficiency was accompanied by high fever. After withdrawal of the drug, the temperature rapidly normalized, whereas serum creatinine continued to rise for about 3 days and then fell back towards previous levels. We conclude that transplant biopsies are of great value in distinguishing between a foscarnet nephrotoxic effect and CMV nephritis, various forms of rejection, and other causes of impaired renal function.

Adult↗
PubMed2003

Synthesis of 3'- and 5'-nitrooxy pyrimidine nucleoside nitrate esters: "nitric oxide donor" agents for evaluation as anticancer and antiviral agents.

A group of 3'-O-nitro-2'-deoxyuridines, 3'-O-nitro-2'-deoxycytidines, and 5'-O-nitro-2'-deoxyuridines possessing a variety of substituents (H, Me, F, I) at the C-5 position were synthesized for evaluation as anticancer/antiviral agents that have the ability to concomitantly release cytotoxic nitric oxide (*NO). Although these compounds generally released a greater percent of *NO than the reference drug isosorbide dinitrate upon incubation in the presence of l-cysteine, or serum, their cytotoxicity (CC(50) = 10(-3) to 10(-6) M range) was comparable to 5-iodo-2'-deoxyuridine, but weaker than 5-fluoro-2'-deoxyuridine, against a variety of cancer cell lines. No differences in cytotoxicity against nontransfected (KBALB, 143B), and the corresponding transfected (KBALB-STK, 143B-LTK) cancer cell lines possessing the herpes simplex virus type 1 (HSV-1) thymidine kinase gene (TK(+)) were observed, indicating that expression of the viral TK enzyme did not provide a gene therapeutic effect. These nitrate esters were inactive antiviral agents except for 5-iodo-3'-O-nitro-2'-deoxyuridine that showed modest activity against HSV-1, HSV-2, and vaccinia virus.

Animals↗
PubMedDate not supplied

Plant antiviral agents, VI. Isolation of antiviral phenolic glucosides from Populus cultivar Beaupre by droplet counter-current chromatography.

Bioassay-guided isolation of the 80% EtOH extract of the leaves of Populus cultivar Beaupré by means of dccc afforded four known phenolic glucosides. Salicin and salireposide were shown to be, at least partially, responsible for the antiviral activity of the extract against poliomyelitis and Semliki forest viruses.

Antiviral Agents↗