In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine
Keyaerts et al.,
In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine,
Biochem. Biophys. Res. Comm., 323:1, 8 October 2004, doi:10.1016/j.bbrc.2004.08.085 (In Vitro)
In Vitro study, SARS-CoV-1, not included in the study count or percentages. IC
50 of CQ for antiviral activity (8.8) is significantly lower than cytostatic activity CC
50 (261.3), selectivity index of 30. IC
50 for inhibition of SARS-CoV
in vitro approximates the plasma concentrations of CQ reached during treatment of acute malaria. CQ may be considered for immediate use in the prevention and treatment of SARS-CoV infections.
14 In Vitro studies support the efficacy of HCQ
[Andreani, Clementi, Dang, Delandre, Faísca, Hoffmann, Liu, Ou, Purwati, Sheaff, Wang, Wang (B), Yao, Yuan].
Keyaerts et al., 28 Aug 2004, peer-reviewed, 5 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: BBRC
Biochemical and Biophysical Research Communications 323 (2004) 264–268
www.elsevier.com/locate/ybbrc
In vitro inhibition of severe acute respiratory syndrome coronavirus
by chloroquine
Els Keyaerts, Leen Vijgen, Piet Maes, Johan Neyts, Marc Van Ranst*
Rega Institute for Medical Research, University of Leuven, 3000 Leuven, Belgium
Received 11 August 2004
Available online 28 August 2004
Abstract
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 lM) was significantly lower than its cytostatic activity; CC50 (261.3 ± 14.5 lM), 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
5 h 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.
Ó 2004 Elsevier Inc. All rights reserved.
Keywords: SARS-CoV; Severe acute respiratory syndrome; Coronavirus; Chloroquine; Antiviral activity
Severe acute respiratory syndrome (SARS) has recently emerged as a new highly contagious human disease with a major impact all over the world [1]. The
global SARS epidemic started in the Guangdong Province in southern China, where several cases of atypical
pneumonia of unknown etiology were reported at the
end of November 2002. A novel member of the Coronaviridae family has been identified as the causative agent
of SARS [2–7]. Three other human coronaviruses
(HCoV) OC43, 229E, and the recently characterized
NL63 are important causes of upper respiratory tract illnesses. In late fall and winter they are responsible for
approximately one-third of the common colds.
During the epidemic in 2003, treatment of SARS was
empirical due to the limited understanding of this new
disease. Protease inhibitors (lopinavir/ritonavir) in combination with ribavirin may be of benefit as antiviral
*
Corresponding author. Fax: +32 16 347900.
E-mail address: Marc.VanRanst@uz.kuleuven.ac.be (M.V. Ranst).
0006-291X/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.bbrc.2004.08.085
therapy, when given in the early phase of the illness
[8,9]. The role of interferon and systemic steroids in preventing immune-mediated lung injury requires further
investigation [10,11].
Since the epidemic, a lot of effort has been put into
antiviral research to find compounds effective against
SARS-CoV. Glycyrrhizin (an active component of
liquorice roots), niclosamide (an antihelminthic drug),
nelfinavir (a human immunodeficiency deficiency virus
(HIV) protease inhibitor), and SNAP (a nitric oxide donor) were reported to have an antiviral effect against
SARS-CoV [12–15].
Savarino et al. [16] hypothesized that chloroquine
might be of some use for the clinical management of
SARS. Chloroquine is known as an antimalarial agent
and elicits also antiviral effects against several viruses
including HIV type 1 (HIV-1) [17–19], hepatitis B virus
[20], herpes simplex virus..
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