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  • Antiviral Agents
  • ScienceDirect Journals (Elsevier)  (13)
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  • 1
    Language: English
    In: Antiviral Research, 1995, Vol.27(4), pp.405-418
    Description: Antiviral activity of L-ascorbic acid-2-phosphate (ASC-2P), a long-acting derivative of L-ascorbic acid, against several human cytomegalovirus (CMV) strains was examined in cultures of human foreskin fibroblasts (HFF) and endothelial cells (EC). ASC-2P at concentrations ranging from 0.2 to 2 mM had no effect on the number of cells expressing 72 kDa CMV immediate early antigen (IEA) while it inhibited expression of 68 kDa late antigen (LA) in infected cultures of both cell types (30% and 55% reduction for EC and HFF, respectively). In HFF cells, virus yield was reduced up to 4-fold, when ASC-2P was added after CMV infection. Antiviral effects were significantly increased in cultures pretreated with ASC-2P. In HFF and EC pretreated for three subcultures (18 days) with 0.2 mM ASC-2P, a significant reduction of cells expressing IEA (75% and 80% reduction in EC and HFF, respectively) and LA (92% and 90% reduction for EC and HFF, respectively) was observed. Pretreatment for three subcultures with ASC-2P inhibited virus yield 50- to 100- fold in EC and 100- to 1000-fold in HFF. The continuous presence of ASC-2P was not required for its antiviral activity. A significantly higher reduction of virus replication with ganciclovir and foscarnet was obtained in ASC-2P pretreated cells than in untreated controls. The results showed that ASC-2P provides L-ascorbic acid with long-lasting antiviral activity against CMV. ASC-2P may be of benefit for the adjunctive treatment of CMV infection.
    Keywords: Human Cytomegalovirus ; L-Ascorbic Acid 2-Phosphate ; Ganciclovir ; Foscarnet ; Medicine ; Biology
    ISSN: 0166-3542
    E-ISSN: 1872-9096
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  • 2
    Language: English
    In: Phytomedicine, 2011, Vol.18(5), pp.384-386
    Description: The extract EPs 7630 is an approved drug for the treatment of acute bronchitis in Germany. The postulated mechanisms underlying beneficial effects of EPs 7630 in bronchitis patients include immunomodulatory and cytoprotective effects, inhibition of interaction between bacteria and host cells, and increase of cilliary beat frequency on respiratory cells. Here, we investigated the influence of EPs 7630 on replication of a panel of respiratory viruses. Determination of virus-induced cytopathogenic effects and virus titres revealed that EPs 7630 at concentrations up to 100 μg/ml interfered with replication of seasonal influenza A virus strains (H1N1, H3N2), respiratory syncytial virus, human coronavirus, parainfluenza virus, and coxsackie virus but did not affect replication of highly pathogenic avian influenza A virus (H5N1), adenovirus, or rhinovirus. Therefore, antiviral effects may contribute to the beneficial effects exerted by EPs 7630 in acute bronchitis patients.
    Keywords: Pelargonium Sidoides ; Respiratory Viruses ; Acute Bronchitis ; Medicine ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0944-7113
    E-ISSN: 1618-095X
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  • 3
    Language: English
    In: Antiviral Research, January 2013, Vol.97(1), pp.41-48
    Description: ► 22 Flavonoids were examined for activity against H5N1 influenza A viruses. ► Biochanin A and baicalein exerted the highest potency. ► Biochanin A and baicalein interfered with H5N1 replication. ► Biochanin A and baicalein interfered with virus-induced cytokine expression. ► Biochanin A and baicalein differ in their molecular antiviral mechanisms. From a panel of 22 flavonoids, we identified six compounds (apigenin, baicalein, biochanin A, kaempferol, luteolin, naringenin) that inhibited influenza A nucleoprotein production in human lung epithelial (A549) cells infected with the highly pathogenic avian influenza H5N1 virus strain A/Thailand/Kan-1/04 in non-toxic concentrations. Baicalein ( : 18.79 ± 1.17 μM, selectivity index 5.82) and biochanin A ( 8.92 ± 1.87 μM, selectivity index 5.60) were selected for further experiments. Both compounds reduced H5N1 infectious titres (baicalein 40 μM: 29-fold reduction, biochanin A 40 μM: 55-fold reduction after infection at MOI 0.01), virus-induced caspase 3 cleavage, nuclear export of viral RNP complexes, and enhanced the effects of the neuraminidase inhibitor zanamivir. Biochanin A and baicalein also inhibited the replication of the H5N1 strain A/Vietnam/1203/04. Time of addition experiments indicated that both compounds interfere with H5N1 replication after the adsorption period. Further mechanistic investigations revealed clear differences between these two flavonoids. Only baicalein interfered with the viral neuraminidase activity (39 ± 7% inhibition at 100 μM, the maximum concentration tested). In contrast to baicalein, biochanin A affected cellular signalling pathways resulting in reduced virus-induced activation of AKT, ERK 1/2, and NF-kB. Moreover, biochanin A inhibited the virus-induced production of IL-6, IL-8, and IP-10 while baicalein inhibited IL-6 and IL-8 production without affecting IP-10 levels. In primary human monocyte-derived macrophages, only baicalein but not biochanin A impaired H5N1 virus replication. Both flavonoids interfered with the H5N1-induced production of IL-6, IP-10, and TNF-α but not of IL-8 in macrophages. These findings indicate that closely related flavonoids can exert anti-H5N1 effects by different molecular mechanisms.
    Keywords: H5n1 ; Biochanin A ; Baicalein ; Antiviral ; Anti-Inflammatory ; Flavonoid ; Medicine ; Biology
    ISSN: 0166-3542
    E-ISSN: 1872-9096
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  • 4
    Language: English
    In: Biochemical Pharmacology, 15 January 2010, Vol.79(2), pp.188-197
    Description: Ribavirin, a broad-spectrum anti-viral drug, exhibits immunomodulatory activities. To study direct effects of ribavirin on natural killer (NK) cell effector functions and signaling, resting NK cells and interleukin (IL)-15-activated NK cells were treated for 5 days with therapeutic ribavirin concentrations ranging from 5 μg/ml to 20 μg/ml. Both resting and IL-15-activated NK cells that were not treated with ribavirin were used as control. Cytotoxicity assays, flow cytometry, enzyme linked immunosorbent assays, and Western blot experiments were performed to elucidate ribavirin effect on NK cells. Results showed that ribavirin (not toxic at concentrations tested; IC 〉 80 μg/ml) had no influence on lysis of target cells by freshly isolated NK cells. Conversely, ribavirin dose-dependently inhibited lysis of target cells by up to 66% and impaired interferon gamma production when IL-15-activated NK cells were used. IL-15-induced increased expression and hence function of NK cell activating receptors including NKp30, NKp44, NKp46 and NKG2D were selectively down-regulated and impaired. These inhibitory effects were associated with the down-regulation of IL-15 receptor beta and gamma expression. Accordingly, downstream events involved in NK cell signaling via IL-15 receptors including the activation of Janus kinase (Jak)-1, signal transducer and activator of transcription STAT-1, STAT-3, and STAT-5 as well as pathways responsible for NK cell degranulation including extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) were impaired. These results reveal a novel mechanism by which ribavirin exerts its immunomodulatory activities.
    Keywords: Nk Cell Activating Receptors ; Nk Cell Signaling ; Nk Cell Degranulation ; Perforin and Granzyme B Release ; Il-15 Receptors ; Pharmacy, Therapeutics, & Pharmacology ; Chemistry
    ISSN: 0006-2952
    E-ISSN: 1873-2968
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  • 5
    Language: English
    In: Biochemical Pharmacology, 01 February 2010, Vol.79(3), pp.413-420
    Description: The antioxidant N-acetyl- -cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells. NAC at concentrations ranging from 5 to 15 mM reduced H5N1-induced cytopathogenic effects (CPEs), virus-induced apoptosis and infectious viral yields 24 h post-infection. NAC also decreased the production of pro-inflammatory molecules (CXCL8, CXCL10, CCL5 and interleukin-6 (IL-6)) in H5N1-infected A549 cells and reduced monocyte migration towards supernatants of H5N1-infected A549 cells. The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-κB and mitogen activated protein kinase p38. Pharmacological inhibitors of NF-κB (BAY 11-7085) or p38 (SB203580) exerted similar effects like those determined for NAC in H5N1-infected cells. The combination of BAY 11-7085 and SB203580 resulted in increased inhibitory effects on virus replication and production of pro-inflammatory molecules relative to either single treatment. NAC inhibits H5N1 replication and H5N1-induced production of pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.
    Keywords: Ros ; NAC ; Cytokines ; H5n1 ; Apoptosis ; Pharmacy, Therapeutics, & Pharmacology ; Chemistry
    ISSN: 0006-2952
    E-ISSN: 1873-2968
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  • 6
    Language: English
    In: Biochemical and Biophysical Research Communications, 2005, Vol.326(4), pp.905-908
    Description: Initial in vitro investigations demonstrated type I interferons (IFNs: IFN-α, IFN-β) to inhibit replication of SARS coronavirus (SARS-CoV), but found the nucleoside analogue ribavirin ineffective in Vero cells. In this report, ribavirin was shown to inhibit SARS-CoV replication in five different cell types of animal or human origin at therapeutically achievable concentrations. Since clinical anti-SARS-CoV activity of type I interferons or ribavirin is limited, we investigated the combination of IFN-β and ribavirin. Determination of the virus yield indicated highly synergistic anti-SARS-CoV action of the combination suggesting the consideration of ribavirin plus IFN-β for the treatment of SARS.
    Keywords: Human Primary Epithelial Kidney Cells ; Caco2 ; Cl14 ; Ma104 ; Vero ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0006-291X
    E-ISSN: 1090-2104
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  • 7
    Language: English
    In: Journal of Ethnopharmacology, 2008, Vol.120(1), pp.108-111
    Description: Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by the SARS coronavirus (SARS-CoV). The development of new antiviral agents for SARS-CoV is an important issue. We tried to find potential resource from Traditional Chinese medicine (TCM) for development of new drugs against SARS-CoV. Our team recruited the potential TCM formulae (also known as Kampo) from two TCM books, Shang-Han Lun (Discussion of Cold-Induced Disorders) and Wen-Bing Tiau-Bein (Differential Management of Febrile Diseases). Several herbs, which were believed to be beneficial for SARS by experienced TCM doctors were also recruited. In addition, a vegetable polular in Taiwan, China and Malaysia, the tender leaf of Roem (also known as Cedrela sinensis, belongs to the family Meliacceae) was also recruited under the suggestion of botanic experts. These TCM products and plant extrats were then tested for the effectiveness against SARS-CoV in vitro. Only TSL-1, the extract from tender leaf of Roem was found to have an evident effect against SARS-CoV with selectivity index 12∼17. This paper reports for the first time that extract from a vegetable, the tender leaf of Roem, can inhibit SARS-CoV in vitro. Thererfore, the tender leaf of Roem may be an important resource agninst SARS-CoV.
    Keywords: Sars ; Herb ; Traditional Chinese Medicine (Tcm) ; Toona Sinensis Roem ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-8741
    E-ISSN: 1872-7573
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  • 8
    Language: English
    In: Antiviral Research, 1997, Vol.33(3), pp.165-175
    Description: An l -glutamine antagonist, 6-diazo-5-oxo- l -norleucin ( l -DON), inhibits replication of vesicular stomatitis virus, poliovirus and paramyxoviruses in cultured cells. We tested the antiviral activity of l -DON against different strains of herpes simplex virus type 1 (HSV-1) in Vero cells. In the presence of a physiological plasma concentration of l -glutamine (0.5 mM) l -Don inhibited 50% production of virus plaques at concentrations ranging from 7.9 to 16 μ M. At concentrations of 40 μ M l -Don inhibited infectious virus yield by 99%. The antiviral activity of l -DON decreased with increasing l -glutamine concentrations. A concentration of 5000 μ M of l -Don had no significant effects on the viability of Vero cells. Transmission electron microscopical investigations showed that l -DON prevented mainly envelopment of viral nucleocapsids in the cytoplasm. The immunoprecipitation experiments demonstrated selective inhibition of synthesis of HSV-1 glycoproteins in l -DON treated cells. The results showed that l -DON inhibits HSV-1 replication at a late stage in the virus replication cycle, probably the cytoplasmic maturation of virions and subsequent virion egress from the cells.
    Keywords: Hsv ; Acyclovir ; 6-Diazo-5-Oxo- L-Norleucin ; Virus-Resistance ; Medicine ; Biology
    ISSN: 0166-3542
    E-ISSN: 1872-9096
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  • 9
    Language: English
    In: Biochemical and Biophysical Research Communications, 2004, Vol.318(3), pp.719-725
    Description: A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.
    Keywords: Severe Acute Respiratory Syndrome ; Coronavirus ; HIV Protease Inhibitor ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0006-291X
    E-ISSN: 1090-2104
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  • 10
    Language: English
    In: Transplant Immunology, 1995, Vol.3(4), pp.313-320
    Description: Desferrioxamine (DFO), commonly used in therapy as a chelator of ferric ion in disorders of iron overload, is a potent inhibitor of human cytomegalovirus (HCMV) replication in cultured fibroblast cells. Moreover, DFO has immunomodulatory activity both in vitro and in vivo. We studied DFO effects on HCMV replication in cultured human endothelial cells and on the expression of several cell surface molecules, which mediate interactions of endothelial cells with other cell types in the immune system. The concentrations of DFO required for 50% reduction in the number of endothelial cells expressing HCMV late antigen, ranged for several HCMV strains from 5.2 to 8.8 mu M. DFO concentrations ranging from 5 to 40 mu M inhibited cellular DNA synthesis in a dose-dependent manner without any significant effects on the cell viability. DFO at 10 mu M concentration suppressed expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1), while it had no significant effect on the expression of vascular cell adhesion molecule-1 (VCAM-1). Expression of HLA class I and class II was not influenced by DFO treatment. The results showed that DFO is both effective in inhibition of HCMV replication and expression of ICAM-1 and ELAM-1 in endothelial cells, a combination that warrants attention to its potential use to prevent HCMV-induced allograft rejection in transplant recipients.
    Keywords: Medicine ; Biology
    ISSN: 0966-3274
    E-ISSN: 1878-5492
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