Anti-herpes activity of the total alkaloid fraction from the branches of Fusaea longifolia (Annonaceae)

ABSTRACT The herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) occur worldwide. Infections caused by these viruses have great public health importance due to the growing resistance to the first-choice drug, acyclovir, especially in immunosuppressed patients. Alkaloids derived from species of Annonaceae have been reported as antiviral agents against HSV and others viruses. Within this context, we evaluated the antiviral activity of the total alkaloid fraction (TAF) extracted from the branches of Fusaea longifolia (Aubl.) Saff. (Annonaceae), a species native to the Amazon region, against the HSV-1 and HSV-2 viruses. The antiviral activity was evaluated through the plate reduction assay and the mode of action was investigated by a set of other assays. The TAF was active against the HSV-2 strain 333 and against the HSV-1 strains KOS and 29R (acyclovir resistant), with selectivity index values (SI = 50% cytotoxic concentration/50% effective concentration) of 5, 4 and 3, respectively. In the preliminary study of the anti-HSV-2 mode of action, TAF showed viral inhibitory effects if added up to 12 h post-infection, had virucidal activity and did not present viral inhibition in pre-treatment. Our results showed that the TAF exhibited anti-HSV activity. Regarding HSV-2, TAF acted after the viral infection and had virucidal activity. A mass spectrometry analysis revealed the presence of nine alkaloids in the TAF that had previously been reported for Annonaceae, including liriodenine, lysicamine and isoboldine, which have been described as potential anti-HSV-1 agents. RESUMO Os vírus herpes simplex tipo 1 (HSV-1) e tipo 2 (HSV-2) têm ampla ocorrência global. As infecções causadas por esses vírus têm grande importância em saúde pública devido à crescente resistência ao fármaco de primeira linha, aciclovir, principalmente em pacientes imunossuprimidos. Alcaloides derivados de espécies de Annonaceae têm sido relatados como agentes antivirais contra o HSV e outros vírus. Neste contexto, nós avaliamos a atividade antiviral da fração alcaloide total (TAF) dos ramos de Fusaea longifolia (Aubl.) Saff. (Annonaceae), uma espécie nativa da região amazônica, contra os vírus HSV-1 e HSV-2. A atividade antiviral foi avaliada através do ensaio de redução em placa e o modo de ação foi investigado por um conjunto de ensaios. O TAF foi ativo contra a cepa HSV-2 333 e contra as cepas HSV-1 KOS e 29R (resistente ao aciclovir), com valores de índice de seletividade (IS = 50% concentr