Will Killer Peptide Offer New Therapy Against Swine Flu H1N1 Virus?

The 2009 swine flu outbreak in humans was caused by a new strain of influenza A virus subtype H1N1. The origin of this new strain is unknown, and the World Organization for Animal Health (OIE) reports that this strain has not been isolated in pigs.

This is a version of the swine flu hemagglutinin amino acid sequence:

MKAILVVMLYTFATANADTLCIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDKHNGKLCK

LRGVAPLHLGKCNIAGWILGNPECESLSTASSWSYIVETSSSDNGTCYPGDFIDYEELRE

QLSSVSSFERFEIFPKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLSK

SYINDKGKEVLVLWGIHHPSTSADQQSLYQNADAYVFVGSSRYSKKFKPEIAIRPKVRDQ

EGRMNYYWTLVEPGDKITFEATGNLVVPRYAFAMERNAGSGIIISDTPVHDCNTTCQTPK

GAINTSLPFQNIHPITIGKCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIEGGWTG

MVDGWYGYHHQNEQGSGYAADLKSTQNAIDEITNKVNSVIEKMNTQFTAVGKEFNHLEKR

IENLNKKVDDGFLDIWTYNAELLVLLENERTLDYHDSNVKNLYEKVRSQLKNNAKEIGNG

CFEFYHKCDNTCMESVKNGTYDYPKYSEEAKLNREEIDGVKLESTRIYQILAIYSTVASS

LVLVVSLGAISFWMCSNGSLQCRICI

The H1N1 swine flu can be transmitted from human to human and causes normal influenza symptoms, such as fever, coughing, and headache. The emergence of swine flu has raised concerns of a pandemic outbreak. Although vaccination can be an effective strategy for preventing infection, it takes at least a few months to develop antiviral drugs.

Researchers have described a killer decapeptide (KP) with killer action against influenza A virus. This killer decapeptide represents the functional internal image of a yeast (Pichia anomala) killer toxin with antimicrobial and anti-human-immunodeficiency-virus-type-1 (HIV-1) activity. After treatment with a KP concentration of 4ug/ml, the scientists observed the complete inhibition of virus particle production and a marked reduction of the synthesis of viral proteins (membrane protein and hemagglutinin, in particular). Moreover, mice infected with influenza A/NWS/33 (H1N1) virus were inoculated with KP (100ug/mouse) once a day for ten days resulting in an improved survival rate of 40% and significantly decreased viral levels in their lungs.

It has been suggested that this peptide could be used to treat swine flu, but the matter needs further study. The KP is an anti-idiotypic antibody-derived (KT-scFv) peptide. Killer decapeptide exerted a strong fungicidal activity against Candida albicans, which was attributed to peptide interactions with beta-glucan. The fact that this polysaccharide is also a critical component of the cryptococcal cell wall, may explain KP's inhibitory activity. All of this suggests that KP may have therapeutic effects against pathogenic microorganisms, HIV-1, and influenza A virus, all by different mechanisms of action.

Synthetic peptides have been widely used in the search for therapeutic peptides. A synthetic peptide antigen corresponding to a region of the glycoprotein gp41 encoded by the env gene of HIV-2 was found to be immunologically reactive with HIV-2-specific antibodies. This is useful in assays for the detection of HIV-2 infection or exposure and in compositions meant to elicit the production of antibodies against HIV-2 in animals, including humans.

The specificity of peptides has tremendous clinical value and makes them very attractive therapeutics. More than 40 therapeutic peptides are in use and about 270 peptides are in clinical trials. In addition, more than 400 peptides are in advanced preclinical phases. These trends suggest that the therapeutic peptide represents a novel therapeutic strategy in clinical settings. We may hope that scientists will son have an answer to the headlining question, "Will killer peptide offer new therapy against swine flu H1N1 virus?"

References:

G. Conti, W. Magliani, S. Conti, L. Nencioni, R. Sgarbanti, A.T. Palamara, L. Polonelli. Therapeutic activity of an anti-idiotypic antibody-derived killer peptide against influenza A virus experimental infection. Antimicrobial Agents and Chemotherapy, 52. 12: 4331-4337

Peptides and Obesity Control!

No single agent has been proven to reduce body weight by more than 10%. However, researchers have found that single molecules can be tailored to simultaneously activate more than one of the body's mechanisms for the safe normalization of body weight.

Glucagon and GLP-1 are peptide hormones best known for their insulin and glucose counter-regulatory actions. Scientists have generated a set of high-potency glucagon-based co-agonist peptides. After weekly administration of PEGylated peptides, it was found that these peptides were highly effective in lowering adiposity and improving glucose tolerance of diet-induced obese mice. Peptides with balanced co-agonism proved especially efficacious, and within only a few weeks of therapy, there was an apparent normalization of body weight and blood glucose.

Reference:

Day JW, etc. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat Chem Biol. 2009 Oct;5(10):749-57. Epub 2009 Jul 13.