Prevention of Experimental Coronavirus Colds with Intranasal  -2b Interferon

Turner, Ronald B.; Felton, Alma; Kosak, Kenneth; Kelsey, Douglas K.; Meschievitz, Carlton

doi:10.1093/infdis/154.3.443

Cited by 86 publications

(58 citation statements)

References 12 publications

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“…The activity of human interferon-a on monkey cells using different viruses in various investigations has been found to be much lower than the corresponding activity on human cells and greatly varying with the type of virus used (11 Á/13). The present results are therefore compatible with the possibility that the SARS-CoV is highly sensitive to the activity of human IFN-a, a possibility that is also suggested by the results of clinical studies on the effect of interferons on other human coronaviruses (14,15).…”

Section: Discussionsupporting

confidence: 90%

In vitro inhibition of SARS virus replication by human interferons

Dahl

Linde

Strannegård

2004

Scandinavian Journal of Infectious Diseases

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Four different types of human interferon, interferon-beta (IFN-beta), recombinant IFN-alpha2a and IFN-alpha2b and natural IFN-alpha were tested for antiviral activity against SARS-coronavirus. The experiments were performed using in vitro cultivated monkey Vero E6 cells. IFN-beta was found to be the most highly active antiviral agent, followed by natural IFN-alpha, whereas the 2 recombinant IFN-alpha2 species were poorly active in the system used. These results suggest that IFN-beta as well as natural IFN-alpha may be used for the treatment of SARS.

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Section: Discussionsupporting

confidence: 90%

In vitro inhibition of SARS virus replication by human interferons

Dahl

Linde

Strannegård

2004

Scandinavian Journal of Infectious Diseases

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“…The present report has indicated the daily dose that should be evaluated, 2.5 x 106 IU. No effect against influenza virus should be expected, although some amelioration of symptoms of parainfluenza or coronavirus infection might be anticipated (13,20). The schedule of administration is still in some question.…”

Section: Discussionmentioning

confidence: 99%

Demonstration of dose-response relationship in seasonal prophylaxis of respiratory infections with alpha-2b interferon

Monto

Albrecht

Schwartz

1988

Antimicrob Agents Chemother

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Recombinant alpha-2b interferon was evaluated in two controlled trials, each lasting for 2 months or more, with different dose levels and schedules of administration. The first study was conducted during a period of transmission of type A (HlNl) and type B influenza. At 2.5 x 106 IU per day, no effect on influenza infection could be detected, but there appeared to be an effect on rhinovirus isolation. During the subsequent autumn 1.7 x 106 IU per day was found to have only a minimal effect on rhinovirus infection (efficacy from 22 to 27%). Under similar circumstances the preceding year, but with a daily dose of 3.0 x 106 IU, efficacy had been 76%. Since there was no evidence of change in rhinovirus strains circulating or their interferon susceptibility, this represented a dose-response relationship. It was possible to evaluate side effects in the 1,200 individuals involved. A lower dose was associated with lower frequency,of symptoms of blood-tinged mucus. Persons using a placebo spray had a higher frequency of this side effect than an observed control. Using the spray 5 days a week was no less likely to produce symptoms than everyday use. Once-daily use was less likely to produce side effects than twice-daily use. There was no indication of sensitization when interferon was used for two separate periods of 4 weeks.

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“…IFNs inhibit viral infection by directly interfering with viral replication and by inducing both an innate and adaptive immune response to infection. IFN-αs are effective in the treatment of hepatitis B and C [7,8] and respiratory coronavirus infections unrelated to the Urbani strain of SARS-CoV [9][10][11][12]. , and combinations of 18] are effective in inhibiting SARS-CoV replication in vitro.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the antiviral effects of interferon-α against a SARS-like coronoavirus infection in vitro

et al. 2006

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Cell Research | www.cell-research.com Antiviral effects of IFN-α against MHV-1 220 npg ORIGINAL ARTICLE IntroductionIn March 2003, a number of laboratories independently reported the isolation and characterization of a novel coronavirus (CoV) from specimens of patients with severe acute respiratory syndrome (SARS) [1,2]. Although an effective therapeutic strategy against SARS has yet to be developed, interferons (IFN) are recognized to play critical roles in host resistance to viral infection [3][4][5][6], thereby implicating them as potential candidates for SARS CoV treatment. IFNs inhibit viral infection by directly interfering with viral replication and by inducing both an innate and adaptive immune response to infection. IFN-αs are effective in the treatment of hepatitis B and C [7,8] and respiratory coronavirus infections unrelated to the Urbani strain of SARS-CoV [9][10][11][12]. , and combinations of 18] are effective in inhibiting SARS-CoV replication in vitro. Moreover, it was reported that macacque monkeys were protected from infection with SARS CoV by treatment with .IFN alfacon-1 (Infergen, Intermune Corp, Brisbane, California), a synthetic IFN-α designed to represent a consensus , has been shown in both cell culture systems [21] and comparative clinical trials [22] to inhibit viral replication more potently than other IFN-αs. Based on these findings, a pilot study to evaluate the potential clinical benefit and safety of IFN alfacon-1 in SARS treatment was conducted by our laboratory. Interferon (IFN)-αs bind to and activate their cognate cell surface receptor to invoke an antiviral response in target cells. Well-described receptor-mediated signaling events result in transcriptional regulation of IFN sensitive genes, effectors of this antiviral response. Results from a pilot study to evaluate the clinical efficacy of IFN-α treatment of SARS patients provided evidence for IFN-inducible resolution of disease. In this report we examined the contribution of IFN-inducible phosphorylation-activation of specific signaling effectors to protection from infection by a SARS-related murine coronavirus, MHV-1. As anticipated, the earliest receptor-activation event, Jak1 phosphorylation, is critical for IFN-inducible protection from MHV-1 infection. Additionally, we provide evidence for the contribution of two kinases, the MAP kinase p38MAPK, and protein kinase C (PKC) d to antiviral protection from MHV-1 infection. Notably, our data suggest that MHV-1 infection, as for the Urbani SARS coronoavirus, inhibits an IFN response, inferred from the lack of activation of pkr and 2'5'-oas, genes associated with mediating the antiviral activities of IFN-αs. To identify potential target genes that are activated downstream of the IFN-inducible signaling effectors we identified, and that mediate protection from coronavirus infection, we examined the gene expression profiles in the peripheral blood mononuclear cells of SARS patients who received IFN treatment. A subset of differentially regulated genes were distinguished with...

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Prevention of Experimental Coronavirus Colds with Intranasal -2b Interferon

Cited by 86 publications

References 12 publications

In vitro inhibition of SARS virus replication by human interferons

In vitro inhibition of SARS virus replication by human interferons

Demonstration of dose-response relationship in seasonal prophylaxis of respiratory infections with alpha-2b interferon

Characterization of the antiviral effects of interferon-α against a SARS-like coronoavirus infection in vitro

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