Novel ionophores active against La Crosse virus identified through rapid antiviral screening

Zachary J. Sandler; Michelle N. Vu; Vineet D. Menachery; Bryan C. Mounce

-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.01.21.914929 doi: bioRxiv preprint Valinomycin activity alters host cell activity. We thus hypothesized that valinomycin's antiviral 194 activity was due to its effect on the cell. The role of potassium in bunyavirus infection has been 195 well-documented, and bunyavirus entry is potassium dependent 21, 22 . To test if valinomycin was 196 affecting the cell rather than the virus, we treated Huh7 cells with 2 µM valinomycin and, 197 immediately before infection, we washed away the drug. As a control, we maintained valinomycin 198 on cells or replaced the valinomycin after washing away the initial treatment. We observed that 199 even after removing and washing valinomycin from the cells, the antiviral activity persisted, as 200 viral titers remained reduced to the same level as when valinomycin treatment is concurrent with 201 infection ( Figure 4D ). Together, these data suggest that valinomycin does not directly inactivate 202 viral particles but that treatment of cells reduces LACV infection, potentially by disrupting 203 potassium-dependent entry. 204