In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds.
Effective antiviral agents are urgently needed to combat the possible return of severe acute respiratory syndrome (SARS). Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. The two interferons were only active if the cell lines were pre-incubated with the drugs 16 h before viral inoculation. Results were confirmed by plaque reduction assays. Antiviral activity varied with the use of different cell lines. Checkerboard assays for synergy were performed showing combinations of interferon beta-1a or leukocytic interferon-alpha with ribavirin are synergistic. Since the clinical and toxicity profiles of these agents are well known, they should be considered either singly or in combination for prophylaxis or treatment of SARS in randomised placebo controlled trials in future epidemics.
Chen
F
F
Centre for Research in Plant Drugs Development, Department of Botany, The University of Hong Kong, Pokfulam Road.
Chan
K H
KH
Jiang
Y
Y
Kao
R Y T
RY
Lu
H T
HT
Fan
K W
KW
Cheng
V C C
VC
Tsui
W H W
WH
Hung
I F N
IF
Lee
T S W
TS
Guan
Y
Y
Peiris
J S M
JS
Yuen
K Y
KY
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002726:Chlorogenic Acid / Q000737:chemistry / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D019695:Glycyrrhizic Acid / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D000068556:Interferon beta-1a; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D061466:Lopinavir; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011744:Pyrimidinones / Q000494:pharmacology; D012254:Ribavirin / Q000494:pharmacology; D012299:Rimantadine / Q000494:pharmacology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*; D045169:Severe Acute Respiratory Syndrome / Q000821:virology; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D005419:Flavonoids; D016898:Interferon-alpha; D011744:Pyrimidinones; D012299:Rimantadine; D061466:Lopinavir; D002726:Chlorogenic Acid; C038044:baicalin; D012254:Ribavirin; D019695:Glycyrrhizic Acid; D016899:Interferon-beta; D000068556:Interferon beta-1a