The mannose-specific plant lectins from Cymbidium hybrid and Epipactis helleborine and the ( N-acetylglucosamine) n-specific plant lectin from Urtica dioica are potent and selective inhibitors of human immunodeficiency virus and cytomegalovirus replication in vitro

Abstract

A series of four mannose(Man)-, three N-acetylglucosamine (GlcNAc) n-, ten N-acetylgalactosamine/galactose(GalNAc/Gal)-, one 5-acetylneuraminic acid(α-2,3-Gal/GalNAc)- and one 5-acetylneuraminic acid(α-2,6-Gal/GalNAc)-specific plant agglutinins were evaluated for their antiviral activity in vitro. The mannose-specific lectins from the orchid species Cymbidium hybrid (CA), Epipactis helleborine (EHA) and Listera ovata (LOA) were highly inhibitory to human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in MT-4, and showed a marked anti-human cytomegalovirus (CMV), respiratory syncytial virus (RSV) and influenza A virus activity in HEL, HeLa and MDCK cells, respectively. The 50% effective concentration (EC 50) of CA and EHA for HIV ranged from 0.04 to 0.08 μg/ml, that is about 3 orders of magnitude below their toxicity threshold (50% inhibitory concentration for MT-4 cell growth: 54 to 60 μg/ml). Also, the (GlcNAc) n-specific lectin from Urtica dioica (UDA) was inhibitory to HIV-1-, HIV-2-, CMV-, RSV- and influenza A virus-induced cytopathicity at an EC 50 ranging from 0.3 to 9 μg/ml. The GalNAc/Gal-, α-2,3-Gal/GalNAc- or α-2,6-Gal/GalNAc-specific lectins were not inhibitory to HIV or CMV at non-toxic concentrations. CA, EHA and UDA proved to be potent inhibitors of syncytium formation between persistently HIV-1- and HIV-2-infected HUT-78 cells and CD4 + Molt/4 (clone 8) cells (EC 50:0.2–2 μg/ml). Unlike dextran sulfate, the plant lectins CA, EHA and UDA did not interfere with HIV-1 adsorption to MT-4 cells and RSV- and influenza A virus adsorption to HeLa and MDCK cells, respectively. They presumably interact at the level of virion fusion with the target cell.