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Arch Virol. 2018 Jun;163(6):1567-1576. doi: 10.1007/s00705-018-3774-1. Epub 2018 Feb 24.

Detection of the antiviral activity of epicatechin isolated from Salacia crassifolia (Celastraceae) against Mayaro virus based on protein C homology modelling and virtual screening.

Author information

1
Departamento de Química, Biotecnologia e Engenharia de Bioprocessos, Universidade Federal de São João del-Rei, Campus Alto Paraopeba, Rodovia MG 443, Km7, Ouro Branco, MG, 36420-000, Brazil.
2
Universidade Federal de São João del-Rei, Campus Centro Oeste Dona Lindu, Rua Sebastião Gonçalves Coelho, 400, Chanadour, Divinópolis, MG, 35501-296, Brazil.
3
Departamento de Química, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Belo Horizonte, MG, 31270-901, Brazil.
4
Núcleo de Estudos em Plantas Medicinais, NEPLAM, Departamento de Química, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Belo Horizonte, MG, 31270-901, Brazil.
5
Departamento de Farmácia, Escola de Farmácia, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil.
6
Departamento de Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil.
7
Departamento de Química, Biotecnologia e Engenharia de Bioprocessos, Universidade Federal de São João del-Rei, Campus Alto Paraopeba, Rodovia MG 443, Km7, Ouro Branco, MG, 36420-000, Brazil. josecarlos@ufsj.edu.br.
8
Núcleo de Estudos em Plantas Medicinais, NEPLAM, Departamento de Química, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Belo Horizonte, MG, 31270-901, Brazil. josecarlos@ufsj.edu.br.

Abstract

Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC50) of 0.247 μmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC50) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.

PMID:
29478125
DOI:
10.1007/s00705-018-3774-1
[Indexed for MEDLINE]

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