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Suppression of Coronavirus Replication by Cyclophilin Inhibitors
Department of Veterinary Hygiene, Veterinary School, Nippon Veterinary & Life Science University, Tokyo 180-8602, Japan
Department of Microbiology and Immunology, Division of Molecular Virology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
* Author to whom correspondence should be addressed.
Received: 18 March 2013; in revised form: 2 May 2013 / Accepted: 8 May 2013 / Published: 22 May 2013
Abstract: 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.
Keywords: cyclophilin; cyclosporin A; coronavirus; NF-AT
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MDPI and ACS Style
Tanaka, Y.; Sato, Y.; Sasaki, T. Suppression of Coronavirus Replication by Cyclophilin Inhibitors. Viruses 2013, 5, 1250-1260.
Tanaka Y, Sato Y, Sasaki T. Suppression of Coronavirus Replication by Cyclophilin Inhibitors. Viruses. 2013; 5(5):1250-1260.
Tanaka, Yoshikazu; Sato, Yuka; Sasaki, Takashi. 2013. "Suppression of Coronavirus Replication by Cyclophilin Inhibitors." Viruses 5, no. 5: 1250-1260.