Fig. 6.

Niclosamide-Ivermectin combination treatments against SARS-CoV-2 in Calu-3 cells. Calu-3 cells were treated for 1 hour with 16 different pairwise combinations of niclosamide and ivermectin. After that, the cells were infected with SARS-CoV-2 at 500 TCID₅₀ for 1 hour. The virus inoculum was discarded, and the cells were further maintained in the medium containing drugs for 2 days. The viral titers were determined using the plaque assay. The dose-response curves of two-drug combination treatments against SARS-CoV-2 are shown; (A) serial dilutions of niclosamide in the presence of different fixed concentrations of ivermectin, (B) serial dilutions of ivermectin in the presence of different fixed concentrations of niclosamide. The synergy scores of two-drug combinations were calculated using SynergyFinderPlus. The dose-response matrix (C) and the Loewe synergy score map of two-drug combination treatment (D) are shown. The synergy scores less than − 10 accounted for the antagonistic effect; from − 10 to 10 accounted for the additive effect; and larger than 10 accounted for the synergistic effect between two drugs. The experiments were repeated at least three times, and data are shown as mean ± SD in A, B and C or mean [95% confidence intervals (CI)] in D