Selection of casticin-resistant LASVrv. (A) The adaptive mutant virus was selected by serially passaging LASVrv in the presence of 6.25 μM casticin. In a parallel experiment, LASVrv passaging in vehicle served as a control. (B) Sequencing chromatograms of viruses from P6 to P10. The asterisk highlights the emergence of the adaptive mutant. (C) Resistant activities to casticin of the WT and F446L LASVpv. Vero cells were treated with casticin at the indicated concentrations; 1 h later, WT or F446L LASVpv (MOI, 0.01) was added to the culture for 1 h. The infected cells were lysed 23 h later, and the luciferase activities were measured. Data are means and SD from 2 or 3 independent experiments. ***, P < 0.001. (D) Amino acid sequence alignment of the mammarenavirus transmembrane domain.