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 microM. 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 Ki values = 8.2 +/- 0.7 and 9.1 +/- 2.4 microM, respectively. Our findings suggest that specific abietane-type diterpenoids and lignoids exhibit strong anti-SARS-CoV effects.
Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, ROC.
Chih-Chun
CC
Wen
Yueh-Hsiung
YH
Kuo
Jia-Tsrong
JT
Jan
Po-Huang
PH
Liang
Sheng-Yang
SY
Wang
Hong-Gi
HG
Liu
Ching-Kuo
CK
Lee
Shang-Tzen
ST
Chang
Chih-Jung
CJ
Kuo
Shoei-Sheng
SS
Lee
Chia-Chung
CC
Hou
Pei-Wen
PW
Hsiao
Shih-Chang
SC
Chien
Lie-Fen
LF
Shyur
Ning-Sun
NS
Yang
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000737:chemistry; D017705:Lignans / Q000737:chemistry; D008958:Models, Molecular; D053978:Pentacyclic Triterpenes; D010946:Plants, Medicinal; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000201:enzymology; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry; D014709:Vero Cells; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D014779:Virus Replication; D000094062:Betulinic Acid
D017705:Lignans; D053978:Pentacyclic Triterpenes; D013729:Terpenes; D014315:Triterpenes; D014764:Viral Proteins; C425325:savinin; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases; D000094062:Betulinic Acid