title: Chloroquine is a potent inhibitor of SARS coronavirus infection and spread.
abstract: 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.
authors.affiliation: Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. mvincent@cdc.gov
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Vincent
authors.forename: Eric
authors.initials: E
authors.lastname: Bergeron
authors.forename: Suzanne
authors.initials: S
authors.lastname: Benjannet
authors.forename: Bobbie R
authors.initials: BR
authors.lastname: Erickson
authors.forename: Pierre E
authors.initials: PE
authors.lastname: Rollin
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Ksiazek
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
mesh_terms: 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
chemical_list: 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