Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31.

Abstract

MAP30 (Momordica anti-HIV protein of 30 kDa) and GAP31 (Gelonium anti-HIV protein of 31 kDa) are anti-HIV plant proteins that we have identified, purified, and cloned from the medicinal plants Momordica charantia and Gelonium multiflorum. These antiviral agents are capable of inhibiting infection of HIV type 1 (HIV-1) in T lymphocytes and monocytes as well as replication of the virus in alreadyinfected cells. They are not toxic to normal uninfected cells because they are unable to enter healthy cells. MAP30 and GAP31 also possess an N-glycosidase activity on 28S ribosomal RNA and a topological activity on plasmid and viral DNAs including HIV-1 long terminal repeats (LTRs). LTRs are essential sites for integration of viral DNA into the host genome by viral integrase. We therefore investigated the effect ofMAP30 and GAP31 on HIV-1 integrase. We report that both of these antiviral agents exhibit dose-dependent inhibition of HIV-1 integrase. Inhibition was observed in all of the three specific reactions catalyzed by the integrase, namely, 3' processing (specific cleavage ofthe dinucleotide GT from the viral substrate), strand transfer (integration), and "disintegration" (the reversal of strand transfer). Inhibition was studied by using oligonucleotide substrates with sequences corresponding to the U3 and U5 regions of HIV LTR. In the presence of 20 ng of viral substrate, 50 ng of target substrate, and 4 ,LM integrase, total inhibition was achieved at equimolar concentrations of the integrase and the antiviral proteins, with EC50 values of about 1 ,uM. Integration of viral DNA into the host chromosome is a vital step in the replicative cycle of retroviruses, including the AIDS virus. The inhibition of HIV-1 integrase by MAP30 and GAP31 suggests that impediment of viral DNA integration may play a key role in the anti-HIV activity of these plant proteins.

Anti-HIV-1 integrase compound fromPometia pinnataleaves

“…(Lauraceae; Zhang et al, 2002); globoidnan from Eucalyptus globoidea Blakely (Myrtaceae; Ovenden et al, 2004), and two proteins, MAP30 and GAP31 from Momordica charantia L. (Cucurbitaceae) and Gelonium multiflorum A. Juss. (Euphorbiaceae), respectively (Lee-Huang et al, 1995).…”

Cochinin B, a Novel Ribosome-Inactivating Protein from the Seeds of Momordica cochinchinensis

“…8) Type I RIPs are highly basic proteins with pI values of 9-10 and display molecular weight of 26-30 kDa. The proteins from the Cucurbitaceae plants exhibit an array of biological activities including anti-HIV-1, 4,9) immunomodulatory, 10) antiproliferative, 10) deoxyribonuclease 11) and ribonuclease. 12) It has recently been described that Momordica cochinchinensis consisted of two isoforms of type I RIPs: namely Momorcochin from root tubers and Momorcochin-S from seeds with molecular mass of approximately 32 kDa and 30 kDa, respectively.…”

Application of Flame Atomic Absorption Spectrometry in Food Biotechnology - <i>Momordica charantia</i> Lin

“…The various constituents of crude bitter melon extract have shown anti-cancer activity and cytotoxic activity against leukemic cell [4]. Alpha and beta-momorcharins have been reported to exhibit HIV virus [5].The antibacterial activity of momordica charantia to treat the bacterial infection [6].…”