Abstract

Dengue is the most important arthropod-borne viral disease worldwide. Infection with any of the four dengue virus (DENV) serotypes can be asymptomatic or lead to disease with clinical symptoms ranging from undifferentiated and self-limiting fever to severe dengue disease, which can be fatal in some cases. Currently, no specific antiviral compound is available for treating DENV. The aim of this study was to identify compounds in plants from Paraguayan folk medicine with inhibitory effects against DENV. We found high virucidal activity (50% maximal effective concentration (EC50) value of 24.97 µg/mL) against DENV-2 in the ethanolic extract of the roots of Solanum sisymbriifolium Lam. (Solanaceae) without an evident cytotoxic effect on Vero E6 cells. Three saponins isolated from the root extract showed virucidal effects (EC50 values ranging from 24.9 to 35.1 µg/mL) against DENV-2. Additionally, the saponins showed inhibitory activity against yellow fever virus (EC50 values ranging from 126 to 302.6 µg/mL), the prototype virus of the Flavivirus genus, suggesting that they may also be effective against other members of this genus. Consequently, these saponins may be lead compounds for the development of antiviral agents.

Highlights

  • Dengue is the most important arthropod-borne viral disease, affecting approximately 390 million people per year, of which 96 million manifest diverse severity in the clinic [1]

  • Non-cytotoxic concentrations of saponin samples and dimethyl sulfoxide (DMSO) were used in the virucidal assay, and the results showed that all of the isolated saponins exerted an inhibitory effect against Dengue virus (DENV)-2 (Figure 5)

  • We found that the ethanolic extract of S. sisymbriifolium roots showed inhibitory activity against DENV-2 without an evident cytotoxic effect in Vero E6 cells

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Summary

Introduction

Dengue is the most important arthropod-borne viral disease, affecting approximately 390 million people per year, of which 96 million manifest diverse severity in the clinic [1]. An estimated 3.9 billion people in 128 countries are at risk of infection with dengue virus [2]. Infection with any of the four DENV serotypes can be asymptomatic or lead to disease with clinical symptoms ranging from an undifferentiated and self-limiting fever to severe dengue disease, which is mostly characterized by plasma leakage and hypovolemic shock that can be fatal in some cases [3]. A vaccine (Dengvaxia, Sanofi-Pasteur, France) against DENV infection received its first marketing authorization in late 2015 and is currently available in several Asian and Latin American countries. Several promising molecules have shown potential anti-DENV effects [5,6,7], no specific antiviral compound is available against this virus. The identification of compounds with an inhibitory effect against DENV is of great interest

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