Cyclophilin A as a target in the treatment of cytomegalovirus infections

• Published in: Antiviral Chemistry and Chemotherapy Vol. 26; p. 2040206618811413
• Main Authors: A Abdullah, Ashwaq, Abdullah, Rasedee, A Nazariah, Zeenathul, N Balakrishnan, Krishnan, Firdaus J Abdullah, Faez, A Bala, Jamilu, Mohd-Lila, Mohd-Azmi
• Format: Book Review Journal Article
• Language: English
• Published: London, England SAGE Publications 2018; Sage Publications Ltd
• Subjects: Antiviral agents; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Cyclophilin A - antagonists & inhibitors; Cyclophilin A - immunology; Cyclophilin A - metabolism; Cyclosporin A; Cytomegalovirus; Cytomegalovirus - drug effects; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - virology; Dose-Response Relationship, Drug; Drug resistance; Immune response; Immunosuppression; Immunosuppressive agents; Latency; Lymphocytes T; Microbial Sensitivity Tests; Molecular Structure; Parasites; Proteins; Replication; Review; Structure-Activity Relationship; Toxicity; Cyclophilins; cyclosporin A; immunosuppressive drug; cytomegalovirus; congenital infection; cyclophilin A
• ISSN: 2040-2066; 0956-3202; 2040-2066
• DOI: 10.1177/2040206618811413

Background Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity. Methods Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins. Results Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug. Conclusion Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.