In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine.
We report on chloroquine, a 4-amino-quinoline, as an effective inhibitor of the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro. Chloroquine is a clinically approved drug effective against malaria. We tested chloroquine phosphate for its antiviral potential against SARS-CoV-induced cytopathicity in Vero E6 cell culture. Results indicate that the IC50 of chloroquine for antiviral activity (8.8 +/- 1.2 microM) was significantly lower than its cytostatic activity; CC50 (261.3 +/- 14.5 microM), yielding a selectivity index of 30. The IC50 of chloroquine for inhibition of SARS-CoV in vitro approximates the plasma concentrations of chloroquine reached during treatment of acute malaria. Addition of chloroquine to infected cultures could be delayed for up to 5h postinfection, without an important drop in antiviral activity. Chloroquine, an old antimalarial drug, may be considered for immediate use in the prevention and treatment of SARS-CoV infections.
Keyaerts
Els
E
Rega Institute for Medical Research, University of Leuven, 3000 Leuven, Belgium.
Vijgen
Leen
L
Maes
Piet
P
Neyts
Johan
J
Van Ranst
Marc
M
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D018075:RNA, Complementary / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy*; D013997:Time Factors; D014709:Vero Cells; D014779:Virus Replication
D000962:Antimalarials; D000998:Antiviral Agents; D018075:RNA, Complementary; D002738:Chloroquine