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Fusion peptide derivatives with antibacterial anti-influenza virus activities

An anti-influenza virus, fusion peptide technology, applied in the direction of antiviral agents, hybrid peptides, antibacterial drugs, etc., can solve the problems of large side effects, easy to produce drug resistance, etc., and achieve the effect of good antibacterial activity

Active Publication Date: 2015-05-20
广州真极和美生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] There are deficiencies in the medicines for the treatment of two types of influenza viruses: wherein amantadine, amantadine and other drugs can only inhibit avian influenza A, are ineffective for avian influenza B, and the side effects of the medication are large, and they only act on the ion channel M2 target point, easy to develop drug resistance
[0016] At present, there are few studies on HA2 as the target to inhibit the entry of influenza virus into the host. Only one group of scientists reported that the polypeptide derived from HA2 and linked to cholesterol can prevent the fusion of avian influenza virus and cell membrane and virus infection

Method used

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  • Fusion peptide derivatives with antibacterial anti-influenza virus activities
  • Fusion peptide derivatives with antibacterial anti-influenza virus activities
  • Fusion peptide derivatives with antibacterial anti-influenza virus activities

Examples

Experimental program
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Effect test

Embodiment 1 1

[0068] Example 1 A Class of Fusion Peptide Derivatives with Antibacterial and Anti-Influenza Virus Activities

[0069] The present invention modifies and transforms the N-terminal fusion peptides of different HA subtypes of influenza viruses to obtain corresponding fusion peptide derivatives with both antibacterial and anti-influenza virus activities.

[0070] 1. Fusion peptide derivatives designed based on the N-terminal 20 amino acid sequence of the truncated fusion peptide

[0071] (1) Obtain fusion peptide derivatives based on the fusion peptide of H3 subtype

[0072] The fusion peptide sequence (23 amino acids) of the H3 subtype is: GLFGAIAGFI E NGW E GMI D GWYG, remove the last three amino acids in the sequence (GLFGAIAGFI E NGW E GMI D G), use lysine (Lys), D-lysine (D -Lys), Monomethyllysine [Lys(Me)], Dimethyllysine [Lys(Me2)], Trimethyllysine [Lys(Me3)], Arginine (Arg), D-arginine (D-Arg), homoarginine (Har), monomethylarginine [Arg(Me)], symmetrical dimethyl...

Embodiment 2

[0146] The relevant experimental methods involved in this embodiment are as follows:

[0147] 1. Strains, cells and culture conditions

[0148] Strains used in this study: Staphylococcus aureus (ATCC12600), Escherichia coli (ATCC25922), Pseudomonas aeruginosa (ATCC25853) and Streptococcus mutans (ATCC25175). All strains were stored in -80°C refrigerator (Microbank vials). Culture conditions: S.aureus and S.mutans were cultured in TH medium (Todd-Hewitt broth) at 37°C, and E.coli and P.aeruginosa were cultured in LB medium (Luria-Bertani broth) at 37°C. Except for S.mutans cultured under anaerobic conditions, the other three bacteria were cultured under aerobic conditions.

[0149] MDCK cells and 293T cells were derived from ATCC, and were incubated with DMEM medium (containing glutamine, 10% FBS) at 37°C, 5% CO 2 cultivated under conditions.

[0150] 2. Peptide synthesis

[0151] Peptides were all synthesized on amide MHBA resin using standard 9-fluorenylmethylcarbonyl Fm...

Embodiment 1

[0227] Fusion peptide derivatives such as GLFGAIAGFI RRG, IKGGWPGLVKGWYG; GLFGAIAGFIRRGWR GMVRGWYG in Example 1 were also studied in related experiments in Example 2, and the results were similar to those of the above fusion peptide derivatives, so we will not repeat them here.

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Abstract

The invention discloses fusion peptide derivatives with antibacterial anti-influenza virus activities. The fusion peptide derivatives are obtained by replacing one part of amino acids with negative charges and uncharged amino acids in the influenza virus fusion peptides by amino acids with positive charges and analogues thereof. The fusion peptide derivatives refer to novel fusion peptides with gram positive bacteria-resistant, gram negative bacteria-resistant and anti-virus effects; and moreover, the fusion peptide derivatives have anti-influenza virus activities, and the aim of preventing influenza viruses from entering the host cells can be achieved by inhibiting comformational change of influenza virus HA2. The multifunctional antimicrobial polypeptides have potential application prospects in virus cold complicated bacterial infection.

Description

technical field [0001] The invention relates to a class of fusion peptide derivatives with both antibacterial and anti-influenza virus activities. Background technique [0002] Influenza virus is an RNA virus that causes influenza in humans, dogs, horses, pigs and poultry. Taxonomically, influenza viruses belong to the family Orthomyxoviridae, which can cause acute upper respiratory tract infections and spread rapidly through the air. There are often periodic pandemics around the world. In mid-December 2003, highly pathogenic avian influenza (HPAI) caused by the H5N1 avian influenza virus (AIV) hit Asia, and swept across South Korea, Japan, In eight East and Southeast Asian countries including China and Indonesia, nearly 100 million birds were killed or eliminated. Of the 348 confirmed cases of human infection reported by the World Health Organization, 216 have died, or 60%. In 2010, the influenza A (H1N1) virus became a pandemic, and more than 18,337 people were killed b...

Claims

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Application Information

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IPC IPC(8): C07K19/00A61P31/04A61P31/16
Inventor 何坚刘叔文王静瑜林冬果武文姣
Owner 广州真极和美生物科技有限公司
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