Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice
Keyaerts et al.,
Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice,
Antimicrob. Agents Chemother, August 2009, 53(8), doi:0.1128/AAC.01509-08
CQ inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with CQ acquired transplacentally or via maternal milk. The highest survival rate (98.6%) was found when mother mice were treated daily with a concentration of 15 mg of CQ per kg of body weight. Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg CQ and 13% survival when treated with 1 mg/kg CQ. CQ can be highly effective against HCoV-OC43 infection in newborn mice and may be considered as a future drug against HCoVs.
Keyaerts et al., 1 Aug 2009, peer-reviewed, 7 authors.
Abstract: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug. 2009, p. 3416–3421
0066-4804/09/$08.00⫹0 doi:10.1128/AAC.01509-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Vol. 53, No. 8
Antiviral Activity of Chloroquine against Human Coronavirus OC43
Infection in Newborn Mice䌤
Els Keyaerts, Sandra Li, Leen Vijgen, Evelien Rysman, Jannick Verbeeck,
Marc Van Ranst,* and Piet Maes
Laboratory of Clinical Virology, Department of Microbiology and Immunology, Rega Institute for Medical Research,
University of Leuven, Leuven, Belgium
Received 12 November 2008/Returned for modification 24 December 2008/Accepted 9 April 2009
Until recently, human coronaviruses (HCoVs), such as HCoV strain OC43 (HCoV-OC43), were mainly
known to cause 15 to 30% of mild upper respiratory tract infections. In recent years, the identification of new
HCoVs, including severe acute respiratory syndrome coronavirus, revealed that HCoVs can be highly pathogenic and can cause more severe upper and lower respiratory tract infections, including bronchiolitis and
pneumonia. To date, no specific antiviral drugs to prevent or treat HCoV infections are available. We
demonstrate that chloroquine, a widely used drug with well-known antimalarial effects, inhibits HCoV-OC43
replication in HRT-18 cells, with a 50% effective concentration (ⴞ standard deviation) of 0.306 ⴞ 0.0091 M
and a 50% cytotoxic concentration (ⴞ standard deviation) of 419 ⴞ 192.5 M, resulting in a selectivity index
of 1,369. Further, we investigated whether chloroquine could prevent HCoV-OC43-induced death in newborn
mice. Our results show that a lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with
chloroquine acquired transplacentally or via maternal milk. The highest survival rate (98.6%) of the pups was
found when mother mice were treated daily with a concentration of 15 mg of chloroquine per kg of body weight.
Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg chloroquine
and 13% survival when treated with 1 mg/kg chloroquine. Our results show that chloroquine can be highly
effective against HCoV-OC43 infection in newborn mice and may be considered as a future drug against
HCoVs.
PHEV was remarkably divergent from HCoV-OC43 and
BCoV (30, 31, 33).
HCoVs cause respiratory infections, but gastroenteritis and
neurological disorders can also occur (3, 20). Until now, five
HCoVs have been described. HCoV-OC43 and HCoV-229E
are responsible for 10 to 30% of all common colds, and infections occur mainly during the winter and early spring (21). In
2003, a novel HCoV displaying only distant antigenic and genetic similarities to the two previously known HCoVs was
identified as the causal agent of SARS, and this causes severe
lung disorder, leading in some cases to systemic infection and
eventually death in about 10% of cases (19). During the two
years after the SARS outbreak, two additional previously unrecognized coronaviruses affecting humans, HCoV-NL63 and
HCoV-HKU1, were identified (29, 35). HCoV-NL63 infection
is related to acute respiratory dysfunction in infected individuals. Furthermore, HCoV-NL63 was identified as the major
pathogen responsible for croup in young children (9, 10, 22).
The clinical features of HCoV-NL63 infections appear to be
more severe than those commonly attributed to infections by
HCoV-OC43 and HCoV-229E (4, 12, 29). Infection with
HCoV-HKU1 is mostly associated with bronchiolitis and pneumonia (35,..
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