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Planta Med 2007; 73(3): 200-205
DOI: 10.1055/s-2007-967109
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

The Alkaloid 4-Methylaaptamine Isolated from the Sponge Aaptos aaptos Impairs Herpes simplex Virus Type 1 Penetration and Immediate-Early Protein Synthesis

Thiago Moreno L. Souza1 , 3 , Juliana L. Abrantes1 , 3 , Rosângela de A. Epifanio2 , Carlos Frederico Leite Fontes3 , Izabel C. P. P. Frugulhetti1
  • 1Laboratório de Virologia Molecular, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil
  • 2Departamento de Química Orgânica, Programa de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Niterói, RJ, Brazil
  • 3Laboratório de Estrutura e Regulação de Proteínas, Programa de Química Biológica, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Further Information

Publication History

Received: October 7, 2006

Accepted: December 22, 2006

Publication Date:
06 February 2007 (online)

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Abstract

We describe in this paper that the alkaloid 4-methylaaptamine, isolated from the marine sponge Aaptos aaptos, inhibited HSV-1 infection. We initially observed that 4-methylaaptamine inhibited HSV-1 replication in Vero cells in a dose-dependent manner with an EC50 value of 2.4 μM. Moreover, the concentration required to inhibit HSV-1 replication was not cytotoxic, since the CC50 value of 4-methylaaptamine was equal to 72 μM. Next, we found that 4-methylaaptamine sustained antiherpetic activity even when added to HSV-1-infected Vero cells at 4 h after infection, suggesting that this compound inhibits initial events during HSV-1 replication. We observed that 4-methylaaptamine impaired HSV-1 penetration without affecting viral adsorption. In addition, the tested compound could inhibit, in an MOI-dependent manner, the expression of an HSV-1 immediate-early protein, ICP27, thus preventing the inhibition of macromolecular synthesis induced by this virus. Our results warrant further investigation on the pharmacokinetics of 4-methylaaptamine and propose that this alkaloid could be considered as a potential compound for HSV-1 therapy.

Key words

Antiviral - alkaloid - in vitro - marine invertebrates

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Izabel C. P. P. Frugulhetti, PhD

Universidade Federal Fluminense

Departamento de Biologia Celular e Molecular

Outeiro de São João Batista s/n°

Centro Niterói

CEP 24210-150

Rio de Janeiro

Brazil

Phone: +55-21-2629-2280

Fax: +55-21-2629-2280

Email: ipaixao@vm.uff.br