Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus

In this study, 221 phytocompounds were evaluated for activity against anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) activities using a cell-based assay measuring SARS-CoV-induced cytopathogenic effect on Vero E6 cells. Ten diterpenoids (1-10), two sesquiterpenoids (11 and 12), two triterpenoids (13 and 14), five lignoids (15-19), curcumin (20), and reference controls niclosamide (21) and valinomycin (22) were potent inhibitors at concentrations between 3.3 and 10 μM. The concentrations of the 22 compounds to inhibit 50% of Vero E6 cell proliferation (CC₅₀) and viral replication (EC₅₀) were measured. The selective index values (SI = CC₅₀/EC₅₀) of the most potent compounds 1, 5, 6, 8, 14, and 16 were 58, >510, 111, 193, 180, and >667, respectively. Betulinic acid (13) and savinin (16) were competitive inhibitors of SARS-CoV 3CL protease with K_i values = 8.2 ± 0.7 and 9.1 ± 2.4 μM, respectively. Our findings suggest that specific abietane-type diterpenoids and lignoids exhibit strong anti-SARS-CoV effects.