Bifonazole suppresses VSV-Spike and SARS-CoV-2 infection in K18-hACE2 mice
(A) Treatment schematic and survival study results. 5 K18-hACE2 mice per group were anesthetized daily and treated intranasally with 0 or 125 μM bifonazole in 10 μL containing 3.25% DMSO. 20 min after the second daily administration of drug, mice were given a lethal dose of 1E6 (left) or 1E7 PFU (right) of VSV-Spike (strain 2). Daily drug administration was terminated 6 days after VSV-Spike administration. (B) Weights were recorded daily, and mice were assessed for wellness. (C) Mice were treated as above with DMSO or 125 or 250 μM bifonazole, and lungs were collected 4 days after VSV-Spike (1E6 PFU) administration (n = 5 per group). qRT-PCR was performed, and VSV-N mRNA levels were quantified and normalized to HPRT. (D) Schematic of treatment. K18-hACE2 mice (10–11 mice/group) were treated intranasally with DMSO or 250 μM bifonazole as prepared in (A). 20 min after the second daily administration of drug, mice were anesthetized and given 2.5E3 PFU SARS-CoV-2. Drug administration was stopped 4 days after virus administration. Weights were recorded daily (n = 10–11 mice, mean ± SEM; black asterisks indicate that two-tailed paired-ratio t test was used to compare the DMSO and 250 μM bifonazole groups; red asterisks indicate two-way ANOVA with Fisher’s LSD test at each time point).