Planta Med 2003; 69(2): 109-112
DOI: 10.1055/s-2003-37715
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Activity of Lectins from Narcissus Species

Susana López1 , Mercedes Armand-Úgon2 , Jaume Bastida1 , Francesc Viladomat1 , José A. Esté2 , Derek Stewart3 , Carles Codina1
  • 1Departament de Productes Naturals, Biologia Vegetal i Edafologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain
  • 2Laboratori de Retrovirologia, Fundació Irsi Caixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona,Badalona, Spain
  • 3Quality Health and Nutrition Programme, Scottish Crop Research Institute, Invergowrie, Dundee, Scotland
Further Information

Publication History

Received: May 10, 2002

Accepted: October 20, 2002

Publication Date:
07 March 2003 (online)

Abstract

Mannose-specific lectins (MSLs) were isolated from bulbs of fifteen wild Narcissus species growing in Spain and assayed for their HIV-1 infection inhibitory activity in MT-4 cells and compared to the Narcissus pseudonarcissus agglutinin (NPA), the commercially available MSL obtained from daffodils. Almost all the tested MSLs were found to be active, showing EC50 values (μg/mL) similar to that of NPA, with some being comparable to those obtained with dextran sulfate without significant cytotoxicity. However, on a molar basis almost all of the MSLs tested exhibited lower EC50 values than dextran sulfate whilst six MSLs had values lower than AZT. The most efficacious anti-HIV-1 activity was exhibited by the Narcissus tortifolious MSL, which was 10- (μg/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 (μg/mL), it was 68-fold more potent on a molar basis. The antiviral indices, a ratio of the concentrations that produce cytotoxicity and HIV-1 replication, were calculated and three of the MSLs, 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 was no significant correlation. It was suggested that this may be due to a dissociation between both activities as a consequence of multiple isolectin composition.

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

References

  • 1 Dalgleish A G, Beverley P CL, Clapham P R, Crawford D H, Greaves M F, Weiss R A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus.  Nature. 1984;  312 763-7
  • 2 Lifson J D, Feinberg M B, Reyes G R, Rabin L, Banapour B, Chakrabarti S, Moss B, Wong-Staal F, Steimer KS Engleman E G. Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein.  Nature. 1986;  323 725-8
  • 3 Balzarini J, Schols D, Neyte J, Van Damme E JM, Peumans W , De Clerq E. α-(1 - 3)- and α-(1 - 6)-d-mannose-specific plant lectins are markedly inhibitory to human immunodeficiency virus and cytomegalovirus infections in vitro .  Antimicrob Agents Chemother. 1991;  35 410-6
  • 4 Davidson E, Forrest J MS, Morrison I M, Stewart D. Mannose-specific lectins from plants as diagnostics, vaccines and tools for the elucidation of viral infection mechanisms in animals. In: Annual Report for the Scottish Crop Research Institute for 1999/2000, Dundee SCRI. 2001.: 125-8
  • 5 Weiler B E, Schröder H C, Stefanovich V, Stewart D, Forrest J MS, Allen L B, Bowden B J, Kreuter M H, Voth R, Müller W EG. Sulphoevernan, a polyanionic polysaccharide, and the Narcissus lectin potently inhibit human immunodeficiency virus infection by binding to viral envelope glycoprotein.  J Gen Virol. 1990;  71 1957-63
  • 6 Marchetti M, Mastromarino P, Rieti S, Seganti L, Orsi N. Inhibition of Herpes simplex, rabies and rubella viruses by lectins with different specificities.  Res Virol. 1995;  146 211-5
  • 7 Astoul C H, Peumans W J, Van Damme E JM, Pierre R. Accessibility of the high-mannose glycans of glycoprotein gp120 from human immunodeficiency virus type 1 probed by in vitro interaction with mannose-binding lectins.  Biochem Biophys Res Commun. 2000;  274 455-60
  • 8 Hayakawa T, Kawamura M, Okamoto M, Baba M, Niikawa T, Takehara S, Serizawa T, Akashi M. Concanavalin A-immobilized polystyrene nanospheres capture HIV-1 virions and gp120: Potential approach towards prevention of viral transmission.  J Med Virol. 1998;  56 327-31
  • 9 Van Damme E JM, Peumans W J, Barre A, Rougé P. Plant lectins: A composite of several distinct families of structurally and evolutionary related proteins with diverse biological roles.  Crit Rev Plant Sci. 1998;  17 575-692
  • 10 Barre A, Van Damme E JM, Peumans W J, Rougé P. Structure-function relationship of monocot mannose-binding lectins.  Plant Physiol. 1996;  112 1531-40
  • 11 López S, Codina C, Bastida J, Viladomat F, Davidson E, Stewart D. Biodiversity of mannose-specific lectins within Narcissus species.  J Agric Food Chem. 2002;  50 2507-13
  • 12 Van Damme E JM, Goldstein I J, Peumans W J. A comparative study of mannose binding lectins from the Amaryllidaceae and Alliaceae.  Phytochemistry. 1991;  30 509-14
  • 13 Van Damme E JM, Goldstein I J, Vercammen G, Vuyisteke J, Peumans W J. Lectins of members of the Amaryllidaceae are encoded by multigene families which show extensive homologies.  Physiol Plant. 1992;  86 245-52
  • 14 Schols D, Pawles R, Desmyter I, De Clercq E. Dextran sulfate and other polyanionic anti-HIV compounds specifically interact with the viral gp120 glycoprotein expressed by T-cells persistently infected with HIV-1.  Virology. 1990;  175 556-61
  • 15 Van Damme E JM, Peumans W J. Developmental changes and tissue distribution of lectin in Galanthus nivalis L. and Narcissus cv. Carlton.  Planta. 1990;  182 605-9
  • 16 Van Damme E JM, Allen A K, Peumans W J. Related mannose-specific lectins from different species of the family Amarylidaceae.  Physiol Plant. 1988;  73 52-7
  • 17 Esté J A, Cabrera C, De Clercq E, Struyf S, Van Damme J, Bridger G, Skerlj R T, Abrams M J, Henson G, Gutierrez A, Clotet B, Schols D. Activity of different bicyclam derivatives against human immunodeficiency virus depends on their interaction with the CXCR4 chemokine receptor.  Mol Pharmacol. 1999;  55 67-73
  • 18 Pauwels R, Balzarini J, Baba M, Snoeck R, Schols D, Herdewijn P, Desmyter J De Clercq E. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds.  J Virol Methods. 1988;  20 309-21
  • 19 Harada S, Koyanagi Y, Yamamoto N. Infection of HTLV-IIIB/LAV in HTLV-I-carrying cells MT-2 and MT-4: an application in a plaque assay.  Science. 1985;  229 563-6
  • 20 Adachi A, Gendelman H E, Koening S, Folks T, Willey R, Rabson A, Martin M A. Production of acquired immunodeficiency syndrome-associated retrovirus in human and non-human cells transfected with an infectious molecular clone.  J Virol. 1986;  59 284-91

Dr. Carles Codina

Department of Natural Products

Plant Biology and Edaphology

Faculty of Pharmacy

University of Barcelona

Av. Joan XXIII, s/n

08028 Barcelona

Catalonia

Spain

Email: ccodina@farmacia.far.ub.es

Fax: +34-93-4029043

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