Biomaterial Database

Selective antiviral activity of synthetic soluble L-tyrosine and L-dopa melanins against human immunodeficiency virus in vitro. 1991

D C Montefiori, and J Y Zhou

Department of Pathology, Vanderbilt University Medical School, Nashville, Tennessee 37232.

Melanins are pigments found in hair, skin, irides of the eye, and brain. Their functions in mammals include protection from exposure to sunlight, camouflage from predators, sexual recognition within species, and possible electron transfer reactants. Most natural melanins exist in an insoluble form, which is one reason there is little information on the biological properties of soluble melanins. Here, synthetic soluble melanins were obtained by chemical oxidation of L-tyrosine or spontaneous oxidation of L-beta-3,4-dihydroxyphenylalanine (L-dopa). Replication of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) was inhibited by soluble melanin in two human lymphoblastoid cell lines (MT-2 and H9) and in phytohemagglutinin-stimulated human T cells. Effective concentrations of 0.15-10 micrograms/ml had no cell toxicity. Melanin blocked infection by cell-free virus and interfered with HIV-induced syncytium formation and cytopathic effects when fusion-susceptible, uninfected cells, were mixed with chronically infected cells. Melanin also impeded the HIV-1 envelope surface glycoprotein, and T cell specific monoclonal antibody leu-3a (CD4), but not leu-5b (CD2), from binding to the surface of MT-2 cells. No effect on HIV-1 reverse transcriptase activity in viral lysates was observed. These results identify a unique biological property of melanin, and suggest that soluble melanins may represent a new class of pharmacologically active substances which should be further investigated for potential therapeutic utility in the treatment of Acquired Immune Deficiency Syndrome (AIDS).

UI	MeSH Term	Description	Entries
D010835	Phytohemagglutinins	Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.	Kidney Bean Lectin,Kidney Bean Lectins,Lectins, Kidney Bean,Phaseolus vulgaris Lectin,Phaseolus vulgaris Lectins,Phytohemagglutinin,Hemagglutinins, Plant,Lectin, Kidney Bean,Lectin, Phaseolus vulgaris,Lectins, Phaseolus vulgaris,Plant Hemagglutinins
D011498	Protein Precursors		Precursors, Protein
D011971	Receptors, Immunologic	Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.	Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003588	Cytopathogenic Effect, Viral	Visible morphologic changes in cells infected with viruses. It includes shutdown of cellular RNA and protein synthesis, cell fusion, release of lysosomal enzymes, changes in cell membrane permeability, diffuse changes in intracellular structures, presence of viral inclusion bodies, and chromosomal aberrations. It excludes malignant transformation, which is CELL TRANSFORMATION, VIRAL. Viral cytopathogenic effects provide a valuable method for identifying and classifying the infecting viruses.	Cytopathic Effect, Viral,Viral Cytopathogenic Effect,Cytopathic Effects, Viral,Cytopathogenic Effects, Viral,Effect, Viral Cytopathic,Effect, Viral Cytopathogenic,Effects, Viral Cytopathic,Effects, Viral Cytopathogenic,Viral Cytopathic Effect,Viral Cytopathic Effects,Viral Cytopathogenic Effects
D004295	Dihydroxyphenylalanine	A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.	Dopa,3,4-Dihydroxyphenylalanine,3-Hydroxy-DL-tyrosine,Dihydroxyphenylalanine Hydrochloride, (2:1),beta-Hydroxytyrosine,3 Hydroxy DL tyrosine,3,4 Dihydroxyphenylalanine,beta Hydroxytyrosine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163	Acquired Immunodeficiency Syndrome	An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.	AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000945	Antigens, Differentiation, T-Lymphocyte	Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.	Antigens, Differentiation, T-Cell,Differentiation Antigens, T-Cell,L3T4 Antigens,Leu Antigens, T-Lymphocyte,T-Cell Differentiation Antigens,T-Lymphocyte Differentiation Antigens,T6 Antigens,Antigens, Differentiation, T Lymphocyte,Differentiation Antigens, T Lymphocyte,Antigens, L3T4,Antigens, T-Cell Differentiation,Antigens, T-Lymphocyte Differentiation,Antigens, T-Lymphocyte Leu,Antigens, T6,Differentiation Antigens, T Cell,Differentiation Antigens, T-Lymphocyte,Leu Antigens, T Lymphocyte,T Cell Differentiation Antigens,T Lymphocyte Differentiation Antigens,T-Lymphocyte Leu Antigens
D000998	Antiviral Agents	Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.	Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral