Bioactive Flavanone Glycoside Isolated from Leaves of <i>Faramea</i> Species Presents Antiviral and Protective Activity against Zika and Mayaro Virus Infection

The high frequency of outbreaks, territorial expansion, and cocirculation of different arboviruses reinforce the necessity of efforts for the development of prevention and therapeutic strategies. We previously characterized an anti-Dengue virus activity of 2S-5-hydroxy-4'-methoxy-flavanone-7-<i>O</i>-β-D-apiofuranosyl-(1→6)-β-d-glucopyranoside, a bioactive flavanone glycoside (FvGly) that could be isolated from leaves of different <i>Faramea</i> species. Here, we investigated the ability of FvGly to inhibit other arboviruses, testing against Zika virus (ZIKV), Mayaro virus (MAYV), and Chikungunya virus infections. We demonstrated that FvGly inhibits ZIKV and MAYV infectious particle release from neuronal (SH-SY5Y) and skeletal muscle (C2C12) cells, respectively, when treated before and after viral infection, without presenting a virucidal effect. Treatment with FvGly also results in protection from virus-induced cell death. In agreement, treatment with FvGly reduced the ZIKV and MAYV RNA loads released after infection, and the expression of envelope protein was tightly inhibited in MAYV-infected C2C12 cells. To get insights about the FvGly mechanism, we used target fishing comparative analysis that predicted iNOS, Akt1, and Mapk14 as targets. Molecular docking also supported the high-affinity binding of FvGly with selected targets, mainly iNOS. Finally, we tested the effect of daily treatment with FvGly in a mouse model of MAYV-induced disease. We observed that treatment reduced clinical signs and muscle lesions compared to untreated infected mouse groups. Taken together, our data indicate that, in addition to Dengue, FvGly treatment also has an antiviral and protective effect against ZIKV and MAYV infection.