von Brunn Albrecht, Ciesek Sandra, von Brunn Brigitte, Carbajo-Lozoya Javier
Max-von-Pettenkofer Institute, Ludwig-Maximilians-Universität, München, Germany; German Center for Infection Research (DZIF), Germany.
German Center for Infection Research (DZIF), Germany; Department of Gastroenterology, Hepatology und Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
Curr Opin Virol. 2015 Oct;14:56-61. doi: 10.1016/j.coviro.2015.08.004. Epub 2015 Aug 27.
Replication of coronaviruses is inhibited in vitro by cyclosporin A, a well-known immunosuppressive drug which binds to cellular cyclophilins thus inactivating their enzymatic cis-trans peptidyl-prolyl isomerase function. Latter is required for proper folding of cellular proteins and of proteins of several viruses. Here, we summarize present knowledge on the role of cyclophilin A during coronavirus replication. We present data on the effect of cyclophilin A single nucleotide polymorphism mutants on the replication of human CoV-229E demonstrating the requirement of proper cyclophilin A function for virus propagation. Results define cellular cyclophilin A as a host target for inhibition of coronaviruses ranging from relatively mild common cold to highly pathogenic SARS-CoV and MERS-CoV viruses with the perspective of disclosing non-immunosuppressive cyclosporin A analogs to broadly inactivate the coronavirus family.
环孢素A可在体外抑制冠状病毒的复制，环孢素A是一种著名的免疫抑制药物，它与细胞亲环蛋白结合，从而使其酶促顺反肽基-脯氨酰异构酶功能失活。后者是细胞蛋白和几种病毒蛋白正确折叠所必需的。在此，我们总结了目前关于亲环蛋白A在冠状病毒复制过程中作用的知识。我们展示了亲环蛋白A单核苷酸多态性突变体对人冠状病毒229E复制影响的数据，证明了亲环蛋白A的正常功能对病毒传播的必要性。研究结果将细胞亲环蛋白A定义为抑制冠状病毒的宿主靶点，这些冠状病毒包括相对温和的普通感冒病毒以及高致病性的严重急性呼吸综合征冠状病毒和中东呼吸综合征冠状病毒，有望揭示非免疫抑制性环孢素A类似物以广泛灭活冠状病毒家族。
