HIV Inhibitor from Thai Bitter Gourd

Abstract

Thai bitter gourd protein (MRK29) was isolated from Momordica charantia ripe fruit and seed. The purification was performed by ammonium sulfate fractionation and gel filtration chromatography. MRK29 possessed one isoelectric point of (pI) ≥ 9, and the time of flight mass spectrum (TOFMS) indicated its molecular weight at 28.6 kD. The twenty amino acid sequence from the N-terminus was in the following order: ¹Asp Val Asn Phe Arg Leu Ser Gly Ala ¹⁰Asp Pro Arg X Tyr Gly Met Phe Ile Glu ²⁰Asp. MRK29 inhibited the HIV-1 reverse transcriptase with 50 % IR at the concentration of 18 μg/ml. MRK29 was concentrated in the 30 - 60 % salt precipitated fraction, at which the concentration of 0.175 μg/ml exerted 82 % reduction of viral core protein p24 expression in HIV-infected cells. MRK29 might have modulatory role on immune cells, because it increased 3-fold TNF activity.

Key words

Thai bitter gourd anti-HIV protein - MRK29 - Momordica charantia L. - Cucurbitaceae - HIV-1 reverse transcriptase inhibitor - anti-HIV protein - immunomodulatory effect

References

• 1 Karunanayake E H, Welihinda J, Sirimanne S R, Sinnadorai G. Oral hypoglycemic activity of some medicinal plants of Sri Lanka.  Journal of Ethnopharmacology. 1984;  11 223-1
• 2 Shibib B A, Khan L A, Rahman R. Hypoglycemic activity of Coccinia indica and Momordica charantia in diabetic rats: depression of the hepatic gluconeogenic glucose-6-phosphatase and fructose-1,6-biphosphatase and elevation of both liver and red cell shunt enzyme glucose-6-phosphate dehydrogenase.  Biochemical Journal. 1993;  292 267-70
• 3 Welihinda J, Karunanayake E H, Sheriff M H, Jayasinghe K S. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes.  Journal of Ethnopharmacology. 1986;  17 277-82
• 4 Khanna P, Jain S C. Hypoglycemic activity of polypeptide-p from a plant source.  Journal of Natural Products. 1981;  44 648
• 5 Tomasi L F, Fiume G C, Barbieri L, Stirpe F. Effect of ribosome-inactivating proteins on virus-infected cells. Inhibition of virus multiplication and of protein synthesis.  Archives of Virology. 1982;  71 323-32
• 6 Ng T B, Liu W K, Sze S F, Yeung H W. Action of alpha-momorcharin, a ribosome-inactivating protein, on culture tumor cell lines.  General Pharmacology. 1994;  25 75-7
• 7 Ng T B, Liu W K, Sze S F, Yeung H W. Proteins with abortifacient, ribosome-inactivating, immunomodulatory, antitumor and anti-AIDS activities from Cucurbitaceae plants.  General Pharmacology. 1992;  23 579
• 8 Leung S O, Yeung H W, Leung K N. The immunosuppressive activities of two abortifacient proteins isolated from the seeds of bitter melon (Momordica charantia).  Immunopharmacology. 1987;  13 159
• 9 Schinazi R F. Progress in the development of natural products for human immunodeficiency viruses infections. In: Chu CK, Cutler HG, edtiros Natural products as antiviral agents. New York; Plenum Press 1992: 9-10
• 10 Lee-Huang S, Huang P L, Nara P L, Chan H C, Kung H F, Hung P, Huang H I, Huang P L. NAP30: a new inhibitor of HIV-1 infection and replication.  Federation of European Biochemical Societies Letters. 1990;  272 12-8
• 11 Lee-Huang L, Chen H C, Kung H, Huang P L, Nara P L, Li B Q, Huang P, Huang H I, Huang P L. Plants proteins with antiviral activity against human immunodeficiency virus. In: Chu CK, Cutler HG, editors Natural products as antiviral agents. New York; Plenum Press 1992: 153-70
• 12 Lee-Huang L, Huang P L, Nara P L, Chen H C, Kung H, Huang P, Huang H I, Huang P L. A plant protein useful for treating tumors and HIV infection.  PCT Int. Appl. WHO. 92 06;  106 58 pp
• 13 Lee-Huang L, Huang P L, Huang P L, Bourinbaiar A S, Chen H C, Kung H F. Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31.  Proceedings of the National Academy of Sciences of the United States of America. 1995;  92 8818-22
• 14 Bradford M M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.  Analytical Biochemistry. 1976;  72 248-54
• 15 Laemmli U K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.  Nature. 1970;  227 680-5
• 16 Ruft M R, Gifford R E. Purification and physico-chemical characterization of rabbit tumor necrosis factor.  Journal of Immunology. 1980;  125 1671-7
• 17 Minami Y J, Funatsu G. The complete amino acid sequence of momordin-a, a ribosome-inactivating protein from the seeds of bitter gourd (Momordica charantia).  Bioscience Biotechnology and Biochemistry. 1993;  57 1141-4