Abstract

The alphaviruses Chikungunya (CHIKV), Mayaro (MAYV), Una (UNAV), and the flavivirus Zika (ZIKV) are emerging or re-emerging arboviruses which are responsible for frequent epidemic outbreaks. Despite the large impact of these arboviruses on health systems, there are no approved vaccines or treatments to fight these infections. As a consequence, there is an urgent need to discover new antiviral drugs. Natural products are a rich source of compounds with distinct biological activities, including antiviral properties. Thus, we aimed to explore the potential antiviral activity of Ginkgolic acid against the arboviruses CHIKV, MAYV, UNAV, and ZIKV. Viral progeny production in supernatants from cells treated or not treated with Ginkgolic acid was quantified by plaque-forming assay. Ginkgolic acid’s direct virucidal activity against these arboviruses was also determined. Additionally, viral protein expression was assessed using Western blot and immunofluorescence. Our results reveal that Ginkgolic acid promotes a dose-dependent decrease in viral titers in all tested viruses. Moreover, the compound demonstrated strong virucidal activity. Finally, we found that viral protein expression was affected by treatment with this drug. Collectively, these findings suggest that Ginkgolic acid could have broader antiviral activity.

Highlights

  • The Alphavirus (Togaviridae family) and Flavivirus (Flaviviridae family) genera are arthropod-borne viruses with a widespread distribution in tropical and subtropical countries [1].Both genera are enveloped single-stranded RNA viruses of positive polarity with genomes ranging from 10 to 12 kilobases in length [2,3]

  • To examine the effect of Ginkgolic acid on alphavirus replication, we performed a kinetic infection in Vero or HeLa cells

  • The cells were pre-treated with Ginkgolic acid or Dimethyl sulfoxide (DMSO) for 1 h; we removed the medium with the treatments, and the cells were infected with CHIKV, MAYV or UNAV

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Summary

Introduction

The Alphavirus (Togaviridae family) and Flavivirus (Flaviviridae family) genera are arthropod-borne viruses (arboviruses) with a widespread distribution in tropical and subtropical countries [1]. Both genera are enveloped single-stranded RNA viruses of positive polarity with genomes ranging from 10 to 12 kilobases in length [2,3]. Within the Alphavirus genus, 31 species of viruses have been identified and classified into 11 different complexes based on their antigenic characteristics [7,8] According to this classification, CHIKV, Mayaro (MAYV) and Una (UNAV) have been grouped within the Selimki Forest antigenic complex [8].

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