Dados do Trabalho


Título

ANTIVIRAL ACTIVITY OF PLITIDEPSIN (APLIDIN) AGAINST ALL FOUR DENGUE SEROTYPES (DENV 1 - 4)

Introdução

Despite considerable advances in the study of the dengue virus, no broadly applicable anti-dengue drugs are currently available for humans. Therefore, new approaches are necessary for the development of a potent antiviral drug against the dengue virus.

Objetivo (s)

To determine the non-toxic concentrations of Plitidepsin for the Vero cell lineage and to evaluate its potential antiviral activity against all dengue serotypes (1-4) in a post-infection treatment

Material e Métodos

Vero cells were subjected to a cytotoxic analysis under a concentration range of 100 nM to 0.026 nM. Antiviral activity was then evaluated in a screening test, followed by TCID50 virus titter definition and qRT-PCR molecular method

Resultados e Conclusão

The results showed that drug concentrations were safe to maintain at least 50% (CC50) and 80% (CC20) of cell viability. The CC50 was equal to 5.652 nM and the CC20 was equal to 2.617 nM. In addition, we evaluated the Plitidepsin antiviral activity against all dengue serotypes (1-4) and found that it showed a significant inhibitory effect against all dengue serotypes at the CC20 concentration of 2.617 nM. The Inhibitory Concentration (IC50) required to reduce at least 50% of the virus monolayer infection was 0.01774 nM for DENV-1, 0.02640 nM for DENV-2, 0.01686 nM for DENV-3, and 1.608 nM for DENV-4. The drug Selective Index (SI) for each serotype was 318.60 for DENV-1, 214.09 for DENV-2, 335.23 for DENV-3, and 3.514 for DENV-4. Plitidepsin exhibited a significant inhibitory effect against dengue virus infection. However, further investigation, such as determining the action mechanism and conducting in vivo analysis, is necessary to support Plitidepsin as a new anti-dengue therapeutic option.

Palavras-chave

Plitidepsin (Aplidin), Dengue virus, Antiviral

Agradecimentos

PHM.MC - Pharma Mar, S.A, Fiotec - Fundação para o Desenvolvimento Científico e Tecnológico em Saúde

Área

Eixo 08 | Arboviroses

Autores

Poliana Gomes da Silva, Constância Flávia Junqueira Ayres Lopes, Rodrigo Correa Oliveira, Carlos Ernesto Ferreira Starling , Lindomar José Pena