Hypericum perforatum (HP1) acts as an antiviral against ancestral SARS-CoV-2. (A,C) Vero cells were seeded overnight, and on the next day, prior to infection (MOI = 0.05), cells were incubated at 37 °C for 1h with infection-DMEM containing either solvent control (DMSO) or HP1. Concurrently, SARS-CoV-2 was incubated for 1 h at room temperature in infection-PBS that contained either DMSO or HP1. After infection (37 °C/1 h), cells were further incubated in infection-DMEM including either DMSO or HP1. After 24 h, virus supernatants were collected and subjected to plaque assay. (A) Results are expressed as PFU/mL (mean and s.d.), and one-way ANOVA with Dunnett’s multiple comparisons was done by comparing each value with the control. (C) Dose–response curve of the normalized virus titer values as % of solvent control is depicted (mean and s.d.). (B,D–F) Vero cells were seeded overnight, and on the next day, cells were incubated for 24 h with infection-DMEM that contained either solvent control (DMSO) or HP1. After incubation, the MTT assay-based cytotoxicity was measured. (B,E) Cell viability as % of solvent control is shown (mean and s.d.), and one-way ANOVA with Dunnett’s multiple comparisons was done by comparing each value with the control. (D,F) Dose–response curve of the normalized cytotoxicity values as % of solvent control is depicted (mean and s.d.). * for p ≤ 0.05, ** for p ≤ 0.01, and **** for p ≤ 0.0001.