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Influenza a and b virus replication-inhibiting peptides

A technology of influenza virus and inhibitory peptides, applied in the field of influenza virus replication inhibitory peptides

Inactive Publication Date: 2012-05-02
PIKE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is growing concern within the medical community that strains of influenza resistant to these two drugs are rapidly emerging
Older adamantane drugs are ineffective against FluB, and global distribution of oseltamivir-resistant influenza viruses suggests limitations of such drugs

Method used

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  • Influenza a and b virus replication-inhibiting peptides
  • Influenza a and b virus replication-inhibiting peptides
  • Influenza a and b virus replication-inhibiting peptides

Examples

Experimental program
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Embodiment Construction

[0048] Embodiments of the present invention will now be described with the aid of the foregoing figures and accompanying tables, by way of example only.

[0049] Materials and methods

[0050] virus strain

[0051] For infection experiments, A / WSN / 33(H1N1) according to Ghanem et al. (2007), A / Thailand / 1(Kan-1) / 2004 according to Chockephaibulkit et al. (2005), A / Thailand / 1(Kan-1) / 2004 according to Norton (1987) were used. B / Yamagat / 73 and VSV (Indiana serotype) as described by Schwemmle (1995).

[0052] Plasmid construction

[0053] Ghanem (2007), Mayer (2007) and Pleschka (1996) describe the plasmids pCA-Flag-GFP and pCA-PB1 1-25 Expression plasmids for A-GFP, pCA-PB1-HA, FluA minireplicon plasmid and FluB minireplicon. According to Pleschka (1996), by cloning the firefly luciferase ORF (reverse) flanked by the noncoding region of paragraph 8 of B / Yamagata / 73 into the Sapl digested plasmid pPolI-SapI-Rib, thereby Obtain the FluB minigenome expression plasmid pPolI-lucRT_B...

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Abstract

A synthesized or isolated influenza virus replication-inhibiting peptide that competitively inhibits protein-protein interaction of the PA and PB1 of both influenza Virus Types A and B and novel in vitro binding screen to identify peptides with antiviral activity against influenza viruses of both type A and B is disclosed. In addition to the well-known pandemic influenza A viruses (such as the 1918 ''Spanish'' flu or H5N1), both type A and B viruses contribute greatly to the annual recurring epidemics that cause the vast majority of human cases and medical cost. Surprisingly, it was found that the novel virus replication-inhibiting, are able to inhibit protein-protein interaction of the PA and PB1 subunits of the heterotrimeric viral RNA polymerase complex of both influenza virus types A and B. The viral polymerase sub- unit interaction domain turned out as an effective target for the new antivirals, as correct assembly of the three viral polymerase subunits PB1, PB2 and PA is required for viral RNA synthesis and infectivity.

Description

technical field [0001] The present invention relates to influenza virus replication inhibitory peptides which inhibit the replication of influenza A and B viruses; influenza virus replication inhibitors which inhibit influenza virus replication; methods for the determination of inhibitors of influenza virus polymerase subunit interaction and methods comprising Influenza therapeutics of viral replication inhibitory peptides. Background technique [0002] Influenza viruses are negative-strand RNA viruses that cause annual epidemics and recurring epidemics, causing many illnesses and severe economic burdens. With the exception of the well-known influenza A viruses (such as the 1918 "Spanish" flu or H5N1), both A and B viruses are responsible for recurring annual epidemics that cause many illnesses and enormous medical costs. WHO recommends annual vaccination against circulating influenza strains A (FluA) and B (FluB). However, current vaccines do not provide complete protecti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/11A61K38/04
CPCC12N2760/16122A61K38/00C12N2760/16222C07K14/005A61P31/16
Inventor U·喀斯乐D·迈尔K·文德利希C·拉纳德希拉M·施韦姆勒
Owner PIKE PHARMA
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