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

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

Potassium ions play a crucial role in cellular entry; however, a role for sodium or calcium ions is 208 not as well described. Marituba virus (MTBV) infection results in a sodium ion influx 23 , but the 209 origin or function of these ionic changes are not known. To determine if other ionophores might 210 exhibit antiviral activity, we treated cells with increasing doses of nonactin (potassium and sodium 211 ionophore), nigericin (hydrogen and potassium ionophore), calcium ionophore I, and sodium 212 ionophore III ( Figure 5A ). Two hours later, we infected with LACV at MOI 0.01 and measured viral 213 titers at 48 hpi. Both nonactin and nigericin exhibited significant antiviral activity, and viral titers 214 were not measurable above 4 and 1 µM, respectively ( Figure 5B ). Treatment with sodium 215 ionophore III resulted in a dose-dependent decrease in viral titers, and virus was not recovered 216 above 10 µM. Interestingly, treatment with calcium ionophore I showed no changes in viral titer, 217 even at the highest dose. Thus, we observe that LACV replication is disrupted by several 218 ionophores, especially potassium ionophores, highlighting the role for potassium in virus infection. The copyright holder for this preprint (which was not peer-reviewed) is the .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