(A) VeroE6 cells were treated with indicated concentrations (2, 10, 50, and 250 μg/ml) of tannic acid, OPCs, or punicalagin, and cell viability was detected with MTT assay. (B–D) VeroE6 cells with and without TMPRSS2 expression were pretreated with the indicated concentrations (2, 10, and 50 μg/ml) of tannic acid, OPCs, or punicalagin, and then infected with SARS-CoV-2 wild-type Spike Vpps. After 24 hr of infection, the infection efficiency rate was measured according to luciferase activities. All data are shown as mean ± SD (n = 3). (E) Antiviral activity of tannic acid, OPCs, and punicalagin against SARS-CoV-2 Vpps based on (A–D). aCC50 is the median cytotoxic concentration such as the dose causing 50% cell death. bEC50 is the half-maximal effective concentration such as the concentration of a compound required to inhibit SARS-CoV-2 infection by 50%. cSI is the safety index such as the ratio of CC50 to EC50. For CC50, extra-sum-of-squares F-test was performed to evaluate differences of OPC or punicalagion compared to tannic acid. For EC50, extra-sum-of-squares F-test was performed to evaluate differences of tannic acid, OPC, or punicalagin of overexperssing TMPRSS2 cells compared to control cells. The p-values are indicated by asterisks, *p<0.05; **p≤0.01; ***p≤0.001.