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

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.

Antiviral - alkaloid - in vitro - marine invertebrates

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