The alkaloid 4-methylaaptamine isolated from the sponge Aaptos aaptos impairs Herpes simplex virus type 1 penetration and immediate-early protein synthesis.
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 microM. Moreover, the concentration required to inhibit HSV-1 replication was not cytotoxic, since the CC50 value of 4-methylaaptamine was equal to 72 microM. 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.
Souza
Thiago Moreno L
TM
Laboratório de Virologia Molecular, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil. tmoreno@bioqmed.ufrj.br
Abrantes
Juliana L
JL
de A Epifanio
Rosângela
R
Leite Fontes
Carlos Frederico
CF
Frugulhetti
Izabel C P P
IC
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D006561:Herpes Simplex / Q000188:drug therapy; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011161:Porifera; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
C486054:4-methylaaptamine; D000470:Alkaloids; D000998:Antiviral Agents; D009287:Naphthyridines; D010936:Plant Extracts