Suppression of coronavirus replication by cyclophilin inhibitors.

Suppression of coronavirus replication by cyclophilin inhibitors.
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DOI:
10.3390/v5051250
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发表时间:
2013-05-22
期刊:
Viruses
影响因子:
--
通讯作者:
Sasaki T
Sasaki T
中科院分区:
其他
文献类型:
--
作者:
Tanaka Y;Sato Y;Sasaki T

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冠状病毒感染多种哺乳动物和禽类物种,并分别以严重急性呼吸综合征(SARS)、猫传染性腹膜炎(FIP)、小鼠肝炎和禽类传染性支气管炎的形式在人、猫、小鼠和禽类中引起严重疾病。目前还没有针对SARS冠状病毒或FIP病毒的有效疫苗或治疗方法,这两种病毒都能导致致命疾病。据报道,亲环素抑制剂环孢菌素A(CsA)可以抑制冠状病毒的复制。CsA是一种众所周知的免疫抑制药物,其与细胞亲环素结合以抑制钙调磷酸酶,一种钙-钙调蛋白激活的丝氨酸/苏氨酸特异性磷酸酶。钙调磷酸酶的抑制阻断了活化T细胞的核因子从胞质溶胶易位到细胞核中,从而阻止了编码细胞因子如白介素-2的基因的转录。亲环素是具有生理功能的肽基-脯氨酰异构酶,多年来已描述其包括分子伴侣和折叠酶活性。此外,许多病毒需要亲环素进行复制;这些病毒包括人类免疫缺陷病毒、水疱性口炎病毒和丙型肝炎病毒。然而,导致抑制病毒复制的分子机制对于不同的病毒是不同的。本文综述了CsA对冠状病毒复制的抑制作用。
Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA), could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.
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