Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK
Kono et al., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (In Vitro)
Kono et al., Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine:.., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (In Vitro)
CQ significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. CQ affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). p38 MAPK inhibitor, SB203580, inhibits CPE induced by HCoV-229E infection and viral replication.
14 In Vitro studies support the efficacy of HCQ
[Andreani, Clementi, Dang, Delandre, Faísca, Hoffmann, Liu, Ou, Purwati, Sheaff, Wang, Wang (B), Yao, Yuan].
Kono et al., 4 Dec 2007, peer-reviewed, 6 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Available online at www.sciencedirect.com
Antiviral Research 77 (2008) 150–152
Short communication
Inhibition of human coronavirus 229E infection in
human epithelial lung cells (L132) by chloroquine:
Involvement of p38 MAPK and ERK
Masakazu Kono a,b , Koichiro Tatsumi b , Alberto M. Imai a ,
Kengo Saito a , Takayuki Kuriyama b , Hiroshi Shirasawa a,∗
a
Department of Molecular Virology, Chiba University School of Medicine, 1-8-1 Inohana,
Chiba 260-8670, Japan
b Department of Chest Medicine, Chiba University School of Medicine, 1-8-1 Inohana,
Chiba 260-8670, Japan
Received 13 July 2007; accepted 17 October 2007
Abstract
The antiviral effects of chloroquine (CQ) on human coronavirus 229E (HCoV-229E) infection of human fetal lung cell line, L132 are reported.
CQ significantly decreased the viral replication at concentrations lower than in clinical usage. We demonstrated that CQ affects the activation of
p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). Furthermore, p38 MAPK inhibitor, SB203580,
inhibits CPE induced by HCoV-229E infection and viral replication. Our findings suggest that CQ affects the activation of MAPKs, involved in
the replication of HCoV-229E.
© 2007 Elsevier B.V. All rights reserved.
Keywords: Coronavirus; 229E; Chloroquine; p38; MAPK; ERK
Chloroquine (CQ), a diprotic weak base that increases the
pH of acidic vesicles, has been used for the treatment of
malaria and inflammatory diseases, such as rheumatoid arthritis. CQ has antimicrobial effects even against viruses, such as
human immunodeficiency virus type 1 (HIV-1) and SARS-CoV
(Sperber et al., 1993; Savarino et al., 2003; Vincent et al., 2005).
However, the inhibitory effect on SARS-CoV is inactive in vivo
(Barnard et al., 2006), and the detailed mechanisms underlying
the antimicrobial and anti-inflammatory effects of CQ remain
poorly understood.
Coronavirus, an enveloped virus, enters the cytoplasm by
endocytosis and matures in the membrane transport system, such
as the trans-Golgi network (TGN) (Nauwynck et al., 1999; Ng
et al., 2003). ER stress caused by Japanese encephalitis virus
infection induces the activation of p38 mitogen-activated protein
kinase (MAPK) and host cell apoptosis (Su et al., 2002). MAPKs
including ERK, JNK and p38 are involved in cell death (Xia et
∗
Corresponding author.
E-mail address: sirasawa@faculty.chiba-u.jp (H. Shirasawa).
0166-3542/$ – see front matter © 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.antiviral.2007.10.011
al., 1995) play a crucial role in infection of coronaviruses, such
as mouse hepatitis virus and SARS-CoV (Banerjee et al., 2002;
Kopecky-Bromberg et al., 2006).
CQ inhibits the activation of p38 MAPK and cytokine production caused by CpG DNA (Yi and Krieg, 1998). ERK, another
MAPK associated with cell proliferation (Xia et al., 1995), is
also affected by virus infection and CQ (Pleschka et al., 2001;
Weber et al., 2002). In this study, we examined the correlation
between CQ and the activation of p38 MAPK and ERK in human
coronavirus 229E (HCoV-229E) infection, and demonstrated the
involvement of p38 MAPK in the replication of HCoV-229E.
To examine the effect of CQ on the viral replication, virus in the supernatants was quantified by measuring
the HCoV-229E RNA by reverse transcription (RT) realtime PCR. RNA from culture supernatants was extracted
by using the QIAamp Viral RNA Mini Kit (QIAGEN)
according to manufacturer’s instructions and used for..
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