Specific Plant Terpenoids and Lignoids Possess Potent Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus

Abstract

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 (CC 50 ) and viral replication (EC 50 ) were measured. The selective index values (SI ) CC 50 /EC 50 ) 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.

Plant-derived triterpenoids and analogues as antitumor and anti-HIV agents

“…67 Compound 1 is also a competitive inhibitor of the protease (3CL) of SARS-CoV, a highly virulent coronavirus, with a K i value of 8.2 µM. 68 In other experiments, 1 and various C-3 modified analogues showed antimicrobial activity, with inhibitory effects toward Mycobacterium tuberculosis (MIC: 10–109 µM), 30,69 Trichophyton soudanense (MIC: 54.8 µM), and T. mentagrophytes (MIC: 27.4 µM). 70 Compound 1 also inhibited the invasion of Porphyromomas falciparum into erythrocytes, with IC 50 values of 13.8 µM, 71 and blocked the binding effects of heat-labile entero-toxin (LT) of E .…”

Quantitative high-throughput screening identifies inhibitors of anthrax-induced cell death

“…Niclosamide, found here to disrupt heptamer prepore-to-pore conversion in the pH sensitive CHO-CMG2 cell line, eliminated SARS-CoV viral antigen synthesis at modest concentrations (1.56 μM) 22. The mechanism of niclosamide's effect on viral replication is unresolved; though modifications of niclosamide's core 2-chloro-4-nitroaniline substructure lead to inhibitors of the SARS 3CL protease23 (niclosamide had only weak inhibitory activity (IC 50 40 μM) 23,24 against this target). The possibility that niclosamide ( 3 ) does act on V-ATPase is intriguing and may yield insight into its effect on viral entry.…”

Application of essential oils as natural cosmetic preservatives

“…Antiviral activity of different essential oils and isolated monoterpenes were confirmed against Herpes simplex viruses [37], cytomegalovirus [38,39] rhinovirus [40], coronavirus [41] and adenovirus [42]. The mechanism and site of antiviral action are still unclear.…”