Development of antiviral therapy for severe acute respiratory syndrome

Cinatl, Jindrich; Michaelis, Martin; Hoever, Gerold; Preiser, Wolfgang; Doerr, Hans Wilhelm

doi:10.1016/j.antiviral.2005.03.002

Cited by 65 publications

(56 citation statements)

References 183 publications

(201 reference statements)

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“…Glycyrrhizin, a triterpene saponine, is a constituent of licorice root. It has been found to interfere with replication and/or cytopathogenic effect (CPE) induction of many viruses including respiratory viruses, such as respiratory syncytial virus, SARS coronavirus, and influenza viruses [23][24][25][26][27][28]. Moreover, antiinflammatory and immunomodulatory properties were attributed to glycyrrhizin [26].…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced pro-inflammatory cytokine and chemokine expression in human macrophages

Michaelis

Geiler

Naczk

et al. 2010

Med Microbiol Immunol

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Hypercytokinaemia is thought to contribute to highly pathogenic H5N1 influenza A virus disease. Glycyrrhizin is known to exert immunomodulatory and anti-inflammatory effects and therefore a candidate drug for the control of H5N1-induced pro-inflammatory gene expression. Here, the effects of an approved parenteral glycyrrhizin preparation were investigated on H5N1 virus replication, H5N1-induced pro-inflammatory responses, and H5N1-induced apoptosis in human monocyte-derived macrophages. Glycyrrhizin 100 μg/ml, a therapeutically achievable concentration, impaired H5N1-induced production of CXCL10, interleukin 6, and CCL5 and inhibited H5N1-induced apoptosis but did not interfere with H5N1 replication. Global inhibition of immune responses may result in the loss of control of virus replication by cytotoxic immune cells including natural killer cells and cytotoxic CD8(+) T-lymphocytes. Notably, glycyrrhizin concentrations that inhibited H5N1-induced pro-inflammatory gene expression did not affect cytolytic activity of natural killer cells. Since H5N1-induced hypercytokinaemia is considered to play an important role within H5N1 pathogenesis, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.

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Section: Introductionmentioning

confidence: 99%

Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced pro-inflammatory cytokine and chemokine expression in human macrophages

Michaelis

Geiler

Naczk

et al. 2010

Med Microbiol Immunol

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“…6 To date, SARS-CoV 3CL pro inhibitors have been reported from both synthetic peptidyl compound libraries and natural product derived libraries. 7 Inhibitory synthetic compounds include C2-symmetric diols, 8 quinolinecarboxylic acids, 9 isatins, 10 and anilides. 11 Natural-derived inhibitors include betulinic acid, 12 indigo, 13 aloeemodin, 13 luteolin, 7 and quinine-methide triterpenoids; the latter are products of our latest investigation 3CL pro inhibitor from Tripterygium regelii.…”

Section: Introductionmentioning

confidence: 99%

Biflavonoids from Torreya nucifera displaying SARS-CoV 3CLpro inhibition

Ryu

Jeong

Kim

et al. 2010

Bioorganic & Medicinal Chemistry

497

381

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As part of our search for botanical sources of SARS-CoV 3CL(pro) inhibitors, we selected Torreya nucifera, which is traditionally used as a medicinal plant in Asia. The ethanol extract of T. nucifera leaves exhibited good SARS-CoV 3CL(pro) inhibitory activity (62% at 100μg/mL). Following bioactivity-guided fractionation, eight diterpenoids (1-8) and four biflavonoids (9-12) were isolated and evaluated for SARS-CoV 3CL(pro) inhibition using fluorescence resonance energy transfer analysis. Of these compounds, the biflavone amentoflavone (9) (IC(50)=8.3μM) showed most potent 3CL(pro) inhibitory effect. Three additional authentic flavones (apigenin, luteolin and quercetin) were tested to establish the basic structure-activity relationship of biflavones. Apigenin, luteolin, and quercetin inhibited 3CL(pro) activity with IC(50) values of 280.8, 20.2, and 23.8μM, respectively. Values of binding energy obtained in a molecular docking study supported the results of enzymatic assays. More potent activity appeared to be associated with the presence of an apigenin moiety at position C-3' of flavones, as biflavone had an effect on 3CL(pro) inhibitory activity.

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“…Although in the 2 years since the discovery of SARS much has been learnt about its pathogenesis, epidemiology and laboratory diagnosis, progress has been less rapid in other areas, particularly in establishing an antiviral treatment for patients. Steroids with or without ribavirin have been widely employed in the treatment of SARS but have not been very effective [2,3] . However, several studies have reported that type I interferons (IFNs) can inhibit SARS replication in vitro [4] and, specifically, that IFN-␤ exhibits the most potent anti-SARS-CoV activity in Vero cells, showing levels of inhibition at concentrations of 1,000 IU/ml or greater [5][6][7][8] .…”

mentioning

confidence: 99%

The Synergistic Interaction of Interferon Types I and II Leads to Marked Reduction in Severe Acute Respiratory Syndrome-Associated Coronavirus Replication and Increase in the Expression of mRNAs for Interferon-Induced Proteins

Scagnolari¹,

Trombetti²,

Alberelli³

et al. 2006

Intervirology

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Interferon (IFN)-α, -β and -γ have been shown to be only marginally effective against severe acute respiratory syndrome coronavirus (SARS-CoV) replication in Vero cell lines. We investigated the combination of type I IFNs (IFN-α or -β) and IFN-γ for antiviral activity and found that such combinations synergistically inhibited SARS-CoV replication in Vero cells, using yield reduction assay and the isobologram and combination index methods of Chou and Talalay for evaluation. The highly synergistic anti-SARS-CoV action of type I IFNs and IFN-γ parallels the marked increase in 2′-5′-oligoadenylate synthetase and p56 mRNAs following exposure in Vero cells to either IFN-α or -β and IFN-γ compared with the transcriptional levels obtained after stimulation with either IFN alone. These results demonstrate that SARS-CoV, although only moderately sensitive to the antiviral action of the individual types of IFN, is highly sensitive to a combination of type I and II IFNs, which suggests that such combinations may have potential in the treatment of SARS-CoV infections.

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Development of antiviral therapy for severe acute respiratory syndrome

Cited by 65 publications

References 183 publications

Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced pro-inflammatory cytokine and chemokine expression in human macrophages

Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced pro-inflammatory cytokine and chemokine expression in human macrophages

Biflavonoids from Torreya nucifera displaying SARS-CoV 3CLpro inhibition

The Synergistic Interaction of Interferon Types I and II Leads to Marked Reduction in Severe Acute Respiratory Syndrome-Associated Coronavirus Replication and Increase in the Expression of mRNAs for Interferon-Induced Proteins

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