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At least 73 records · Page 4Linked to original sources
PubMed1998

[Development of antiviral therapeutic agents from traditional medicines].

Traditional medicines contain various metabolites derived from nucleic acid, protein, and lipid metabolism. Some of these specific metabolites may recognize the differences between viral and host metabolism resulting in anti-viral activity; hence traditional medicines may be useful sources for new antiviral agents. Traditional medicines can be cheaply obtained and have been orally administered as hot-water extracts. Therefore, they may be used for the prophylactic and therapeutic treatment of viral infection by drinking them, such as coffee or tea. Here we describe how the antiviral activity of traditional medicines was screened in vitro and how their therapeutic antiviral activities were verified in vivo, to obtain traditional antiviral medicines that can be clinically used. Therefore, we have selected 12 herbal extracts, from more than 250 herbal medicines, that exhibit therapeutic activities against cutaneous herpes simplex virus (HSV) type 1 (HSV-1) infection in mice. Four of the 12 augmented the therapeutic efficacy of acyclovir (ACV) in mice and showed potent anti-HSV activity against infection with ACV-resistant HSV-1 mutants in mice. These herbal extracts selectively inhibited viral DNA synthesis and showed a different mode of anti-HSV-1 action from that of ACV. They were also effective against both recurrent HSV and cytomegalovirus infections, without toxicity. Such prophylactic and therapeutic antiviral activities of the traditional medicines were verified by the purification of major active compounds. We could show new indications of traditional medicines as antiviral agents. Thus, the drinking of the extracts, in a daily tea or coffee, may be used for prophylaxis and therapy of diseases caused by herpes virus infection and improve the quality of life.

Animals↗
PubMed2006

HIV-1 RT nonnucleoside inhibitors and their interaction with RT for antiviral drug development.

Non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) have become an inherent component of highly active antiretroviral therapy (HAART) in the treatment of human immunodeficiency virus type 1 (HIV-1) infections. One of the most serious problems associated with NNRTIs is that the virus exhibits resistance to the drug through mutation once the virus is exposed to the drug. New inhibitors effective against these mutants and resistant to new mutations are needed in the treatment of HIV-1 infection. Most mutations are such that larger side chain amino acids are replaced with a smaller side chain. Structural and computational approaches have been used to study the interaction between the NNRTI and RT and the dynamics of wild type mutated RT with and without a bound NNRTI to help understand the mechanism of inhibition and NNRTI resistance. It is still not understood how a NNRTI binding in a pocket, 10 A away the polymerase active site, affects the activity of RT, although several hypotheses have been suggested. Therefore, the focus for the development of next generation NNRTIs has to be the design of compounds with an improved resistance profile. Elucidating the mechanism of the interaction between NNRTI and RT is critical if structure-based drug development for HIV-1 RT is to be successful. This calls for a better understanding of the resistance mechanism by crystallographic and computational studies. This review will take a critical look at the numerous computational studies on HIV-RT and compare those results against the current structural and experimental data available.

Drug Design↗
PubMed1995

New developments in antiviral therapy for chronic hepatitis B infection.

The standard treatment of an HBeAg-positive, HBV-DNA-positive chronic hepatitis B patient is a 16-week course of 10 MU alpha-interferon thrice weekly. However, the overall therapeutic effect, as measured by disappearance of the HBe-antigen, is estimated at 30%. Improvement is possible by better selection of the patient, modifications in the treatment schedule, or combination therapy. In the selection of possible candidates for combination therapy, the second generation nucleoside analogues with activity against hepatitis B are good candidates. In clinical studies, lamivudine and famciclovir are used, both of which can reduce serum HBV-DNA to levels below 1 pg/ml within weeks. The ongoing clinical studies address the efficacy and safety of these drugs after prolonged exposure, in combination with alpha-interferon and around liver transplantation in patients with decompensated liver disease.

2-Aminopurine↗
PubMed2002

The role of viruses in human cancer development and antiviral approaches for intervention.

Viruses are estimated to be linked to at least 15% of human cancers. Hepatitis B and C viruses, human papilloma viruses, Epstein-Barr virus, human herpes virus-8 and human T-cell leukemia virus have been definitively linked to human cancer. A brief overview of the molecular mechanisms of carcinogenesis elucidated for these viruses and antiviral approaches which may provide clues to reducing the occurrence or progression of the resulting virally derived cancers are described.

Antiviral Agents↗
PubMed2005

Effects of HBV gene variations on disease development and antiviral therapy for patients with chronic hepatitis B.

BACKGROUND: Viral variation may change pathogenicity, escape immunity, lead to persistence infection, and cause drug resistance against antiviral therapy. This study was undertaken to investigate the effects of HBV gene variation on the progression of disease and on the efficacy of antiviral therapy for patients with chronic hepatitis B(CHB). METHODS: Hepatitis B virus(HBV) gene mutational sites were detected using gene chip in selected hepatitis B patients. RESULTS: In the patients HBeAg did not show serologic conversion or HBeAg(-)/anti-HBe(+), but their HBV DNA remained positive 24 weeks after alpha-interferon therapy, which was associated with mutations of nt1896, nt1814, nt1762 and nt1764. In the patients, that HBV DNA levels decreased or were undetectable, but rebounded later after antiviral therapy by lamivudine was associated with mutations of aa528 and (or) aa552 (i.e. YMDD mutation),which resulted in lamivudine-resistance. YMDD mutation was prone to occur 52 weeks after lamivudine therapy in some chronic hepatitis B patients (26.4%). Nt1896 mutation was common in most chronic hepatitis B patients (68.5%). Chronic severe hepatitis, cirrhosis, and primary liver carcinoma were related to the mutations of nt1896, nt1762 and nt1764. CONCLUSIONS: HBV gene mutations could aggravate patient's condition and affect the efficacy of antiviral therapy. The regular detection of HBV gene mutation is helpful for identification of disease prognosis and adjustment of therapeutic strategy.

Adult↗
PubMed1991

The effect of total or partial T lymphocyte depletion on susceptibility to influenza virus infection and development of antiviral immunity in lethally irradiated mice reconstituted with immune syngeneic bone marrow grafts.

In a previous study, we showed that lethally irradiated mice reconstituted with bone marrow (BM) enriched with spleen cells obtained from A/PR8/34 influenza virus-immune donors had an improved survival rate compared to the survival seen in recipients of naive BM, immune BM or T cell-depleted BM obtained from immune mice. Our purpose was to determine which cell population was responsible for this effect. We therefore compared the resistance to influenza virus of lethally irradiated BALB/c mice reconstituted with BM from immune donors enriched with 20% spleen cells following either incubation with anti-Thy-1, anti-Lyt-2 or anti-L3T4 monoclonal antibodies prior to transplantation, thereby leading to in vivo depletion of antibody-treated lymphocyte subsets. Mice were infected with influenza virus 1 day after BM transplantation. Equal survival rates were observed in recipients of unmanipulated BM and spleen cells obtained from immune donors and recipients of similar inocula treated with monoclonal anti-helper (L3T4) or anti-cytotoxic/suppressor (Lyt-2) antibodies prior to inoculation. The survival rate of all these groups was increased in comparison with mice receiving anti-Thy-1 treated BM and spleen cells, suggesting that both L3T4 and Lyt-2 T cell subsets play a role in protection against virus infections.

Animals↗