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Planta Med 2011; 77(1): 46-51
DOI: 10.1055/s-0030-1250093
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Manzamine A as a Novel Inhibitor of Herpes Simplex Virus Type-1 Replication in Cultured Corneal Cells

Jayavardhana R. Palem1 , Gautam R. Bedadala1 , Khalid A. El Sayed1 , Shao-chung V. Hsia1
  • 1Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, LA, USA
Further Information

Publication History

received February 24, 2010 revised June 4, 2010

accepted June 7, 2010

Publication Date:
19 July 2010 (online)

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Abstract

This study investigated the putative inhibitory effect of manzamine A on HSV-1 infection. Our results indicated that manzamine A effectively inhibited viral replication and infection in the cell line SIRC, a corneal cell line, at 1 µM. The existing anti-HSV-1 drug acyclovir was analyzed and showed a comparable activity at 50 µM. Plaque assays demonstrated that manzamine A reduced the release of infectious virus by 1011-fold. RTPCR assays indicated that HSV-1 virion host shutoff (vhs) activity and ICP0 transcription were decreased by manzamine A treatment. These results bode well for the development of manzamines as potential leads to reduce viral infection in corneal cells and to prevent HSV-1-induced eye infections such as keratitis.

Key words

manzamine A - herpes simplex virus - corneal cells - acyclovir

References

  • 1 Gold D, Corey L. Acyclovir prophylaxis for herpes simplex virus infection.  Antimicrob Agents Chemother. 1987;  31 361-367
    PubMedSearch in Google Scholar
  • 2 Hamuy R, Berman B. Treatment of herpes simplex virus infections with topical antiviral agents.  Eur J Dermatol. 1998;  8 310-319
    PubMedSearch in Google Scholar
  • 3 Remeijer L, Osterhaus A, Verjans G. Human herpes simplex virus keratitis: the pathogenesis revisited.  Ocul Immunol Inflamm. 2004;  12 255-285
    CrossrefPubMedSearch in Google Scholar
  • 4 Herpetic Eye Disease Study Group . Oral acyclovir for herpes simplex virus eye disease: effect on prevention of epithelial keratitis and stromal keratitis.  Arch Ophthalmol. 2000;  118 1030-1036
    PubMedSearch in Google Scholar
  • 5 Whitley R J, Gnann Jr J W. Acyclovir: a decade later.  N Engl J Med. 1992;  327 782-789
    CrossrefPubMedSearch in Google Scholar
  • 6 Coen D M, Schaffer P A. Two distinct loci confer resistance to acycloguanosine in herpes simplex virus type 1.  Proc Natl Acad Sci USA. 1980;  77 2265-2269
    CrossrefPubMedSearch in Google Scholar
  • 7 Englund J A, Zimmerman M E, Swierkosz E M, Goodman J L, Scholl D R, Balfour Jr H H. Herpes simplex virus resistant to acyclovir. A study in a tertiary care center.  Ann Intern Med. 1990;  112 416-422
    PubMedSearch in Google Scholar
  • 8 Burns W H, Saral R, Santos G W, Laskin O L, Lietman P S, McLaren C, Barry D W. Isolation and characterisation of resistant herpes simplex virus after acyclovir therapy.  Lancet. 1982;  1 421-423
    CrossrefPubMedSearch in Google Scholar
  • 9 Sakai R, Higa T, Jefford C W, Bernardinelli G J. Manzamine A, a novel antitumor alkaloid from a sponge.  J Am Chem Soc. 1986;  108 6404-6405
    Search in Google Scholar
  • 10 El Sayed K A, Kelly M, Kara U A, Ang K K, Katsuyama I, Dunbar D C, Khan A A, Hamann M T. New manzamine alkaloids with potent activity against infectious diseases.  J Am Chem Soc. 2001;  123 1804-1808
    CrossrefPubMedSearch in Google Scholar
  • 11 Hu J F, Hamann M T, Hill R, Kelly M. The manzamine alkaloids.  Alkaloids Chem Biol. 2003;  60 207-285
    PubMedSearch in Google Scholar
  • 12 Edrada R A, Proksch P, Wray V, Witte L, Muller W E, Van Soest R W. Four new bioactive manzamine-type alkaloids from the Philippine marine sponge Xestospongia ashmorica.  J Nat Prod. 1996;  59 1056-1060
    CrossrefPubMedSearch in Google Scholar
  • 13 Rao K V, Donia M S, Peng J, Garcia-Palomero E, Alonso D, Martinez A, Medina M, Franzblau S G, Tekwani B L, Khan S I, Wahyuono S, Willett K L, Hamann M T. Manzamine B and E and ircinal A related alkaloids from an Indonesian Acanthostrongylophora sponge and their activity against infectious, tropical parasitic, and Alzheimer's diseases.  J Nat Prod. 2006;  69 1034-1040
    CrossrefPubMedSearch in Google Scholar
  • 14 Rao K V, Santarsiero B D, Mesecar A D, Schinazi R F, Tekwani B L, Hamann M T. New manzamine alkaloids with activity against infectious and tropical parasitic diseases from an Indonesian sponge.  J Nat Prod. 2003;  66 823-828
    CrossrefPubMedSearch in Google Scholar
  • 15 Peng J, Hu J F, Kazi A B, Li Z, Avery M, Peraud O, Hill R T, Franzblau S G, Zhang F, Schinazi R F, Wirtz S S, Tharnish P, Kelly M, Wahyuono S, Hamann M T. Manadomanzamines A and B: a novel alkaloid ring system with potent activity against mycobacteria and HIV-1.  J Am Chem Soc. 2003;  125 13382-13386
    CrossrefPubMedSearch in Google Scholar
  • 16 Hamann M, Alonso D, Martin-Aparicio E, Fuertes A, Perez-Puerto M J, Castro A, Morales S, Navarro M L, Del Monte-Millan M, Medina M, Pennaka H, Balaiah A, Peng J, Cook J, Wahyuono S, Martinez A. Glycogen synthase kinase-3 (GSK-3) inhibitory activity and structure-activity relationship (SAR) studies of the manzamine alkaloids. Potential for Alzheimer's disease.  J Nat Prod. 2007;  70 1397-1405
    CrossrefPubMedSearch in Google Scholar
  • 17 Mayer A M, Hall M L, Lynch S M, Gunasekera S P, Sennett S H, Pomponi S A. Differential modulation of microglia superoxide anion and thromboxane B2 generation by the marine manzamines.  BMC Pharmacol. 2005;  5 6
    CrossrefPubMedSearch in Google Scholar
  • 18 Ichiba T, Corgiat J M, Scheuer P J, Kelly-Borges M. 8-Hydroxymanzamine A, a beta-carboline alkaloid from a sponge, Pachypellina sp.  J Nat Prod. 1994;  57 168-170
    CrossrefPubMedSearch in Google Scholar
  • 19 Foster T P, Rybachuk G V, Kousoulas K G. Expression of the enhanced green fluorescent protein by herpes simplex virus type 1 (HSV-1) as an in vitro or in vivo marker for virus entry and replication.  J Virol Methods. 1998;  75 151-160
    CrossrefPubMedSearch in Google Scholar
  • 20 Khalil A, El-Sayed K, Belal F, Khalil N Y, Hamann M. Spectrofluorimetric determination of manzamine A in spiked human urine and plasma.  Pharmazie. 2003;  58 385-388
    PubMedSearch in Google Scholar
  • 21 Khanfar M A, Asal B A, Mudit M, Kaddoumi A, El Sayed K A. The marine natural-derived inhibitors of glycogen synthase kinase-3beta phenylmethylene hydantoins: in vitro and in vivo activities and pharmacophore modeling.  Bioorg Med Chem. 2009;  17 6032-6039
    CrossrefPubMedSearch in Google Scholar
  • 22 Shimomura Y. [Herpes simplex virus latency, reactivation, and a new antiviral therapy for herpetic keratitis].  Nippon Ganka Gakkai Zasshi. 2008;  112 247-265
    PubMedSearch in Google Scholar
  • 23 Morfin F, Thouvenot D. Herpes simplex virus resistance to antiviral drugs.  J Clin Virol. 2003;  26 29-37
    CrossrefPubMedSearch in Google Scholar
  • 24 Schek N, Bachenheimer S L. Degradation of cellular mRNAs induced by a virion-associated factor during herpes simplex virus infection of Vero cells.  J Virol. 1985;  55 601-610
    PubMedSearch in Google Scholar
  • 25 Everett R D. ICP0, a regulator of herpes simplex virus during lytic and latent infection.  Bioessays. 2000;  22 761-770
    CrossrefPubMedSearch in Google Scholar
  • 26 Maul G G, Guldner H H, Spivack J G. Modification of discrete nuclear domains induced by herpes simplex virus type 1 immediate early gene 1 product (ICP0).  J Gen Virol. 1993;  74 (Pt. 12) 2679-2690
    CrossrefPubMedSearch in Google Scholar
  • 27 Rayasam G V, Tulasi V K, Sodhi R, Davis J A, Ray A. Glycogen synthase kinase 3: more than a namesake.  Br J Pharmacol. 2009;  156 885-898
    CrossrefPubMedSearch in Google Scholar
  • 28 Wozniak M A, Frost A L, Itzhaki R F. Alzheimer's disease-specific tau phosphorylation is induced by herpes simplex virus type 1.  J Alzheimers Dis. 2009;  16 341-350
    PubMedSearch in Google Scholar
  • 29 Itzhaki R F, Lin W R. Herpes simplex virus type I in brain and the type 4 allele of the apolipoprotein E gene are a combined risk factor for Alzheimer's disease.  Biochem Soc Trans. 1998;  26 273-277
    PubMedSearch in Google Scholar
  • 30 Itzhaki R F, Lin W R, Shang D, Wilcock G K, Faragher B, Jamieson G A. Herpes simplex virus type 1 in brain and risk of Alzheimer's disease.  Lancet. 1997;  349 241-244
    CrossrefPubMedSearch in Google Scholar
  • 31 Hill R T, Hamann M T, Peraud O, Kasanah N. Manzamine-producing actinomycetes. US Patent Application 244938. 2005
    PubMedSearch in Google Scholar

Dr. Shao-chung Hsia

Department of Basic Pharmaceutical Sciences
University of Louisiana at Monroe College of Pharmacy

1800 Bienville Drive

Monroe, LA 71201

USA

Phone: +13 1 83 42 17 47

Fax: +13 1 83 42 17 37

Email: hsia@ulm.edu

Prof. Dr. Khalid El Sayed

Department of Basic Pharmaceutical Sciences
University of Louisiana at Monroe College of Pharmacy

1800 Bienville Drive

Monroe, LA 71201

USA

Phone: +13 1 83 42 17 25

Fax: +13 1 83 42 17 37

Email: elsayed@ulm.edu