Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice
Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice
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DOI：
10.1128/aac.01509-08
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发表时间：
2009-08-01
影响因子：
4.9
通讯作者：
Maes, Piet
中科院分区：
文献类型：
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作者：
Keyaerts, Els;Li, Sandra;Maes, Piet
直到最近，人类冠状病毒 (HCoV)，例如 HCoV 毒株 OC43 (HCoV-OC43)，主要被认为可引起 15% 至 30% 的轻度上呼吸道感染。近年来，包括严重急性呼吸综合征冠状病毒在内的新型HCoV的鉴定表明，HCoV具有高致病性，可引起更严重的上呼吸道和下呼吸道感染，包括细支气管炎和肺炎。迄今为止，还没有专门的抗病毒药物可以预防或治疗 HCoV 感染。我们证明，氯喹是一种广泛使用的药物，具有众所周知的抗疟作用，可抑制 HRT-18 细胞中的 HCoV-OC43 复制，其 50% 有效浓度（+/- 标准偏差）为 0.306 +/- 0.0091 muM，50% 细胞毒性浓度（+/- 标准偏差）为 419 +/- 192.5 muM，导致选择性指数为 1,369。此外，我们研究了氯喹是否可以预防 HCoV-OC43 诱导的新生小鼠死亡。我们的结果表明，新生 C57BL/6 小鼠的致命 HCoV-OC43 感染可以用经胎盘或通过母乳获得的氯喹治疗。当母鼠每天接受浓度为每公斤体重 15 毫克的氯喹治疗时，幼鼠的存活率最高（98.6%）。存活率以剂量依赖性方式下降，用 5 mg/kg 氯喹治疗时存活率为 88%，用 1 mg/kg 氯喹治疗时存活率为 13%。我们的研究结果表明，氯喹可以非常有效地对抗新生小鼠的 HCoV-OC43 感染，并可能被认为是未来对抗 HCoV 的药物。
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 (+/- standard deviation) of 0.306 +/- 0.0091 mu M and a 50% cytotoxic concentration (+/- standard deviation) of 419 +/- 192.5 mu 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.