Identification of natural compounds with antiviral activities against SARS-associated coronavirus.
More than 200 Chinese medicinal herb extracts were screened for antiviral activities against Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay for virus-induced cytopathic effect (CPE). Four of these extracts showed moderate to potent antiviral activities against SARS-CoV with 50% effective concentration (EC50) ranging from 2.4 +/- 0.2 to 88.2 +/- 7.7 microg/ml. Out of the four, Lycoris radiata was most potent. To identify the active component, L. radiata extract was subjected to further fractionation, purification, and CPE/MTS assays. This process led to the identification of a single substance lycorine as an anti-SARS-CoV component with an EC50 value of 15.7 +/- 1.2 nM. This compound has a CC50 value of 14980.0 +/- 912.0 nM in cytotoxicity assay and a selective index (SI) greater than 900. The results suggested that four herbal extracts and the compound lycorine are candidates for the development of new anti-SARS-CoV drugs in the treatment of SARS.
Li
Shi-You
SY
Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 101300, China.
Chen
Cong
C
Zhang
Hai-Qing
HQ
Guo
Hai-Yan
HY
Wang
Hui
H
Wang
Lin
L
Zhang
Xiang
X
Hua
Shi-Neng
SN
Yu
Jun
J
Xiao
Pei-Gen
PG
Li
Rong-Song
RS
Tan
Xuehai
X
D047151:Amaryllidaceae Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019668:Liliaceae / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D010617:Phenanthridines / Q000737:chemistry / Q000494:pharmacology*; D008517:Phytotherapy; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*; D013778:Tetrazolium Salts; D014709:Vero Cells
D047151:Amaryllidaceae Alkaloids; D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D010617:Phenanthridines; D013778:Tetrazolium Salts; C015330:lycorine