Detection of components of RNA viral glycoproteins using a manno

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage

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435 71, 435 792, 435 793, 435 794, 435 795, 435974, 436501, 436515, 436827, 436518, C12Q 1700

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054628539

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BRIEF SUMMARY
This invention relates to an anti-viral material and to methods of its use.
Human immunodeficiency virus (HIV) and human T lymphotropic virus (HTLV) have created serious problems throughout the world and it is very important that an effective means of countering them should be found. A large number of materials have been investigated for anti-HIV activity and some have proved to have positive effect; it is desirable to identify materials having anti-HIV activity so that sufficient quantities can be produced for treatment of patients.
It is known that antiretroviral chemotherapy of patients with acquired immunodeficiency syndrome (AIDS) with dideoxynucleosides, such as azidothymidine (AZT), does help some patients. However, the toxicity of AZT, a compound which presumably inhibits viral DNA polymerase in infected cells, is such that new strategies are needed. One strategy is to develop substances that interfere with viral adsorption and penetration by blocking the CD4 receptor or the viral glycoprotein. It has been shown that dextran sulfate is able to block infection of cells by human immunodeficiency virus type 1 (HIV-1). Subsequently, other sulfated polysaccharides, eg heparin sulfate, chondroitin sulfate and polysulfated polyxylan were found to have anti-HIV activity in vitro. These compounds inhibit virus adsorption and syncytium formation though a direct influence of these drugs on the infectivity of virus could not be demonstrated.
Since the pandemic occurrence of AIDS and ATL (adult T-cell leukaemia) there is an urgent need for the development of a diagnostic that will recognise directly HIV and similar viruses, either intact, or as components, especially in body fluids. These viruses are the probable causes of the above diseases.
It has previously been proposed in Journal of Acquired Immune Deficiency Syndromes 1:453-458 by Muller et al to use D-mannose-specific lectin from Gerardia savaglia in the prevention of infection of H9 cells within HIV-1. This lectin is obtained by extraction from coral. However, it agglutinates human blood cells and is therefore unsuitable as a therapeutic agent.
The following procedures are basically applicable for the detection of HIV-1 and HTLV: hybridisation;
Until now ACA has only been described in principle: an antibody which recognises the virus or a component of the virus is fixed to a solid phase, eg glass or plastic. Subsequently, human material, preferably serum or plasma is brought into contact with the bound antibody. After adequate incubation, the complex of immobilised antibody and virus (or viral components) can be visualised by a labelled virus-specific antibody.
In competitive capture the antibody is pre-incubated with a test solution which may contain virus or viral components, and is then brought into contact with the same virus or its components bound to a solid phase.
We have found that mannose-specific lectin is capable of recognising the virus or its components with precision.


SUMMARY OF THE INVENTION

According to the present invention there is provided an anti-viral material comprising a mannose-specific lectin obtained from a bulb of the plant family Amaryllidaceae in combination with a pharmaceutical carrier.
Further according to the present invention there is provided a mannose-specific lectin obtained from a bulb of the plant family Amaryllidaceae for use as an anti-viral material.
Still further according to the present invention there is provided the use of a mannose-specific lectin obtained from a bulb of the plant family Amaryllidaceae for the the manufacture of a medicament for the treatment of RNA viruses which contain glycoproteins with mannose (alpha-1.fwdarw.3) or (alpha-1.fwdarw.6) mannose linkages, for example HIV or HTLV. These viruses are preferably terminal (alpha-1.fwdarw.3) or internal (alpha-1.fwdarw.6) or terminal (alpha-1.fwdarw.6) linkages.
Still further according to the present invention there is provided a vaccine for protection against a virus, said vaccine being produced by the use of a mannose-specific lectin obtaine

REFERENCES:
Balzarini et al., "Marked Inhibition of Human Immunodeficiencey Virus Type 1 and Type 2 by .alpha.-(1-3)-and .alpha.-(1-6)-D-Mannose -Specific Plant Lectins", Abstract 65 in Antiviral Research Suppl. 1 Apr. 1990 p. 73.
Moore et al "Sensitive Elisa for the gp/20 and gp/60 Surface Glycoproteins of HIV-1" in AIDS Res. Human Retro. vol. 4 No. 5 (1988) pp. 369-379.
Van Damme et al. "Reltaed Mannose-Specific Lectins from Different Species of the Family Amaryllidacaea" in Physiol. Plant. vol. 73 (1988) pp. 52-57.
Weiler et al, "Human Immunodeficiency Virus: Novel Enzyme-Linked Immunoassays for Quantitation of Envelop Glycoprotein 120" in J. Virol. Methods, vol. 32 (1991) pp. 287-301.
Upjohn, (1983) Virology, Upjohn Co. Kalamazoo, Mich. pp. 40-43.
Robinson et al; AIDS Res & HV Retroviruses 3 (3), 1987.
W. Muller et al, "Narcissus and Gerardis Lectins: Tools for the Development of a Vaccine Against AIDS and a New ELISA to Quantify HIV-gp 120" in Lectins Cancer, pp. 27-40, 1991.
Van Damme et al., Chemical Abstracts vol. 109(7), 17 Aug. 1988 p. 275, Abstract No. 5431F.
Muller et al., Journal of Acquired Human Deficiency Syndrome vol. 1(5) pp. 453-458.
Robinson et al., Chemical Abstracts vol. 108(13), 2 Mar. 1988 p. 474 Abstract No. 110641r-and-Aids Research and Human Retroviruses vol. 3(3) 265-82.
Weiler et al. Journal of General Virology vol. 71(9) pp. 1957-1963.
Meruelo et al. Proc. Natl. Acad. Sci USA vol. 85 pp. 5230-5234.

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