title: Genetic deficiency and polymorphisms of cyclophilin A reveal its essential role for Human Coronavirus 229E replication.
abstract: 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.
authors: Max-von-Pettenkofer Institute, Ludwig-Maximilians-Universität, München, Germany; German Center for Infection Research (DZIF), Germany. Electronic address: vonbrunn@mvp.uni-muenchen.de.
authors: Albrecht
authors: A
authors: von Brunn
authors: German Center for Infection Research (DZIF), Germany; Department of Gastroenterology, Hepatology und Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Sandra
authors: S
authors: Ciesek
authors: Max-von-Pettenkofer Institute, Ludwig-Maximilians-Universität, München, Germany; German Center for Infection Research (DZIF), Germany.
authors: Brigitte
authors: B
authors: von Brunn
authors: Max-von-Pettenkofer Institute, Ludwig-Maximilians-Universität, München, Germany; German Center for Infection Research (DZIF), Germany.
authors: Javier
authors: J
authors: Carbajo-Lozoya
mesh_terms: D028941:Coronavirus 229E, Human / Q000502:physiology*; D021984:Cyclophilin A / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D014779:Virus Replication
chemical_list: D021984:Cyclophilin A