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.
A series of four mannose(Man)-, three N-acetylglucosamine (GlcNAc)n-, ten N-acetylgalactosamine/galactose(GalNAc/Gal)-, one 5-acetylneuraminic acid (alpha-2,3-Gal/GalNAc)- and one 5-acetylneuroaminic acid(alpha-2,6-Gal/Gal-NAc)-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 (EC50) of CA and EHA for HIV ranged from 0.04 to 0.08 micrograms/ml, that is about 3 orders of magnitude below their toxicity threshold (50% inhibitory concentration for MT-4 cell growth: 54 to 60 micrograms/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 EC50 ranging from 0.3 to 9 micrograms/ml. The GalNAc/Gal-, alpha-2,3-Gal/GalNAc- or alpha-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 (EC50: 0.2-2 micrograms/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.
Balzarini
J
J
Laboratory of Chemotherapy, Rega Institute for Medical Research, Belgium.
Neyts
J
J
Schols
D
D
Hosoya
M
M
Van Damme
E
E
Peumans
W
W
De Clercq
E
E
D000117:Acetylglucosamine / Q000737:chemistry*; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D016264:Dextran Sulfate / Q000494:pharmacology; D006678:HIV / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects; D037102:Lectins; D008358:Mannose / Q000737:chemistry*; D037121:Plant Lectins; D010946:Plants, Medicinal / Q000737:chemistry*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects; D013696:Temperature; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D037102:Lectins; D037121:Plant Lectins; D016264:Dextran Sulfate; D008358:Mannose; D000117:Acetylglucosamine