Virucidal antiviral activity of Maytenus quadrangulata extract against Mayaro virus: Evidence for the presence of catechins

• Published in: Journal of ethnopharmacology Vol. 311; p. 116436
• Main Authors: Nunes, Damiana Antônia de Fátima, Lopes, Gabriela Francine Martins, Nizer, Waleska Stephanie da Cruz, Aguilar, Mariana G. de, Santos, Felipe Rocha da Silva, Sousa, Grasiely Faria de, Ferraz, Ariane Coelho, Duarte, Lucienir Pains, Brandão, Geraldo Célio, Vieira-Filho, Sidney Augusto, Magalhães, Cintia Lopes de Brito, Ferreira, Jaqueline Maria Siqueira, de Magalhães, José Carlos
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 15-07-2023
• Subjects: Alphavirus; Alphavirus - genetics; Animals; Antiviral activity; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Arbovirus; Catechin - pharmacology; Catechins; Chlorocebus aethiops; Folk medicine; Mammals; Mayaro virus; Maytenus; Maytenus quadrangulata; Medicinal plants; Plant extracts; Vero Cells; Maytenus quadrangulata; Medicinal plants; Catechins; Folk medicine; Mayaro virus; Antiviral activity; Alphavirus; Arbovirus; Plant extracts
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2023.116436

Mayaro virus (MAYV) is an arbovirus endemic to the Amazon region, which comprises the states of the North and Midwest region of Brazil and encompasses the largest tropical forest in the world, the Amazon Forest. The confirmation of its potential transmission by Aedes aegypti and recent cases in Brazil, mainly in large centers in the northern region, led to the classification of Mayaro fever as an emerging disease. Traditional medicine is commonly used to treat various diseases, mainly by local riverside populations. Some species of the genus Maytenus, which have similar morphologies, are popularly used to treat infections and inflammations. In this context, our research group has studied and confirmed the antiviral activity of several plant-derived compounds. However, several species of this same genus have not been studied and therefore deserve attention.
This study aimed to demonstrate the effects of ethyl acetate extracts of leaves (LAE) and branches (TAE) of Maytenus quadrangulata against MAYV.
Mammalian cells (Vero cells) were used to evaluate the cytotoxicity of the extracts. After cell infection by MAYV and the treatment with the extracts, we evaluated the selectivity index (SI), the virucidal effect, viral adsorption and internalization, and the effect on viral gene expression. The antiviral action was confirmed by quantifying the viral genome using RT-qPCR and by analyzing the effect on virus yield in infected cells. The treatment was performed based on the effective concentration protective for 50% of the infected cells (EC50).
The leaves (LAE; EC50 12.0 μg/mL) and branches (TAE; EC50 101.0 μg/mL) extracts showed significative selectivity against the virus, with SI values of 79.21 and 9.91, respectively, which were considered safe. Phytochemical analysis revealed that the antiviral action was associated with the presence of catechins, mainly in LAE. This extract was chosen for the subsequent studies since it reduced the viral cytopathic effect and virus production, even at high viral loads [MOI (multiplicity of infection) 1 and 5]. The effects of LAE resulted in a marked reduction in viral gene expression. The viral title was drastically reduced when LAE was added to the virus before infection or during replication stages, reducing virus production up to 5-log units compared to infected and untreated cells.
Through kinetic replication, MAYV was not detected in Vero cells treated with LAE throughout the viral cycle. The virucidal effect of LAE inactivates the viral particle and can intercept the virus at the end of the cycle when it gains the extracellular environment. Therefore, LAE is a promising source of antiviral agents.
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•Leaf (LAE) and branch (TAE) ethyl acetate extracts of Maytenus quadrangulata against Mayaro virus.•No significant cytotoxicity was observed for LAE and TAE.•LAE has selective and dose-dependent antiviral activity.•LAE has potent virucidal activity, indicating direct action on the viral particle.•First report of antiviral activity of the M. quadrangulata against an arbovirus.