An ivermectin – atorvastatin combination impairs nuclear transport inhibiting dengue infection in vitro and in vivo

Protocol to evaluate the antiviral effect of FDA-approved drugs against dengue virus in Huh7 cells and AG129 mice

“… Adapted from (Palacios-Rápalo et al. 1 ). CRITICAL: Exclude mice that die from causes other than infection.…”

“…AG129 mouse is a lethal model for DENV infection, especially because they are knockout mice for interferon receptors (IFNα/β/γ R−/−), 6 making them an ideal model for the study of drugs with antiviral activity extending mouse survival. In AG129 mice infected with DENV-2 and treated with the vehicle, the mean survival time is 13–14 days (in both females and males) 1 ( Figures 7 A and 7B). These studies showed that mice treated with the IVM+ATV combination extended the mean survival time up to 18 days ( Figure 7 C), delaying the onset of signs of dengue disease ( Figure 7 D).…”

“…The subcellular distribution of cellular and DENV-2 protein during treatment with FDA-approved drugs such as IVM and ATV, which affect the nuclear import of viral and host cellular proteins, 1 was analyzed by confocal microscopy. Nuclear import of the host cellular protein KPNA1 and NS3 or NS5 proteins of DENV-2 was measured by fluorescence nucleus-cytoplasm ratio (Fn/C).…”

“…For complete details on the use and execution of this protocol, please refer to Palacios-Rápalo et al. 1 …”

A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin

“…Particularly, ATO can block the nuclear import of Huh7 cells, promoting the cytoplasmic accumulation of KPNA1 and KPNA2, as well as a nuclear import dependent on these pathways [ 65 ]. Moreover, ATO treatment can block the nuclear import of NS5 polymerase and NS3 viral protease of DENV-2.…”