Introduction Human immunodeficiency virus (HIV) is tropic for T lympho- cytes,monocytesandmacrophages,andothercelltypesthatex- pressthedifferentiationantigensCD4(OKT4A/leu-3a)onthecell surface[1].BoththebindingofHIVtoitstargetcellsandthefu- sion (syncytium formation) between HIV-infected and non-in- fected CD4 cells require a specific interaction between the viral envelope glycoprotein gp120 and the cell surface CD4 molecule [1], [2]. Gp120 is a mannose-rich glycoprotein, and has been showntointeractstronglywithseveraldifferentlectins[3].Plant lectinsareasignificantlyheterogeneousgroupofproteinsclassi- Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Activity of Lectins from Narcissus Species Susana López 1 Mercedes Armand-Úgon 2 Jaume Bastida 1 Francesc Viladomat 1 JosØ A. EstØ 2 Derek Stewart 3 Carles Codina 1 Affiliation 1 DepartamentdeProductesNaturals,BiologiaVegetaliEdafologia,FacultatdeFarmàcia, UniversitatdeBarcelona,Barcelona,Spain 2 LaboratorideRetrovirologia,FundacióIrsiCaixa,HospitalUniversitariGermansTriasiPujol, UniversitatAutònomadeBarcelona,Badalona,Spain 3 QualityHealthandNutritionProgramme,ScottishCropResearchInstitute,Invergowrie,Dundee,Scotland Correspondence Dr.CarlesCodina´DepartmentofNaturalProducts´PlantBiologyandEdaphology´FacultyofPharmacy´ UniversityofBarcelona´Av.JoanXXIII,s/n´08028Barcelona´Catalonia´Spain´ E-mail:ccodina@farmacia.far.ub.es´Fax:+34-93-4029043 Received May10,2002´ Accepted October20,2002 Bibliography PlantaMed2003;69:109±112´GeorgThiemeVerlagStuttgart´NewYork´ISSN0032-0943 Abstract Mannose-specific lectins (MSLs) were isolated from bulbs of fif- teen wild Narcissus species growing in Spain and assayed for their HIV-1 infection inhibitory activity in MT-4 cells and com- pared to the Narcissus pseudonarcissus agglutinin (NPA), the commercially available MSL obtained from daffodils. Almost all the tested MSLs were found to be active, showing EC 50 values (mg/mL) similar to that of NPA, with some being comparable to thoseobtainedwithdextransulfatewithoutsignificantcytotoxi- city.However,onamolarbasisalmostalloftheMSLstestedex- hibited lower EC 50 values than dextran sulfate whilst six MSLs had values lower than AZT. The most efficacious anti-HIV-1 ac- tivitywasexhibitedbythe Narcissus tortifolious MSL,whichwas 10- (mg/mL) and 100- (molarity) fold more potent than dextran sulfate. Significantly, although this MSL was 15-fold less potent than AZT in terms of quantity (mg/mL), it was 68-fold more po- tentonamolarbasis.Theantiviralindices,aratiooftheconcen- trations that produce cytotoxicity and HIV-1 replication, were calculatedandthreeoftheMSLs, N. confusus, N. leonensis and N. tortifolius reported 1.5-, 2- and 8.5-fold greater AI values than dextran sulfate or AZT. Comparison of MSL haemagglutination activities (HAA) to their anti-HIV-1 activities showed that there wasnosignificantcorrelation.Itwassuggestedthatthismaybe duetoadissociationbetweenbothactivitiesasaconsequenceof multiple isolectin composition. Keywords Anti-HIV-1 activity ´ mannose-specific lectins ´ Narcissus ´ Ama- ryllidaceae´cytotoxicity Abbreviations MSLs: mannose-specific lectins NPA: Narcissus pseudonarcissus agglutinin AZT: azidotimidine GNA: Galanthus nivalis agglutinin MTT: 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide HAA: haemoagglutination activity Original Paper 109 Heruntergeladen von: Universidad de Barcelona. Urheberrechtlich geschützt.