Chloroquine is a potent inhibitor of SARS coronavirus infection and spread.
BACKGROUND
Severe acute respiratory syndrome (SARS) is caused by a newly discovered coronavirus (SARS-CoV). No effective prophylactic or post-exposure therapy is currently available.


RESULTS
We report, however, that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells. These inhibitory effects are observed when the cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage. In addition to the well-known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations.


CONCLUSIONS
Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds.
Vincent
Martin J
MJ
Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. mvincent@cdc.gov
Bergeron
Eric
E
Benjannet
Suzanne
S
Erickson
Bobbie R
BR
Rollin
Pierre E
PE
Ksiazek
Thomas G
TG
Seidah
Nabil G
NG
Nichol
Stuart T
ST
D000643:Ammonium Chloride / Q000494:pharmacology; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000494:pharmacology*; D019084:Fluorescent Antibody Technique, Indirect; D006031:Glycosylation; D008562:Membrane Glycoproteins / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control / Q000821:virology; D064370:Spike Glycoprotein, Coronavirus; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism
D000998:Antiviral Agents; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; D000643:Ammonium Chloride; D002738:Chloroquine; D007703:Peptidyl-Dipeptidase A; D000085962:Angiotensin-Converting Enzyme 2