title: Cyclophilin inhibitors as antiviral agents.
abstract: Cyclophilins (Cyps) are ubiquitous proteins that effect the cis-trans isomerization of Pro amide bonds, and are thus crucial to protein folding. CypA is the most prevalent of the ~19 human Cyps, and plays a crucial role in viral infectivity, most notably for HIV-1 and HCV. Cyclophilins have been shown to play key roles in effective replication of a number of viruses from different families. A drug template for CypA inhibition is cyclosporine A (CsA), a cyclic undecapeptide that simultaneously binds to both CypA and the Ca(2+)-dependent phosphatase calcineurin (CN), and can attenuate immune responses. Synthetic modifications of the CsA scaffold allows for selective binding to CypA and CN separately, thus providing access to novel, non-immunosuppressive antiviral agents.
authors.affiliation: SCYNEXIS Inc., Research Triangle Park, NC 27709, USA. mike.peel@scynexis.com
authors.forename: Michael
authors.initials: M
authors.lastname: Peel
authors.forename: Andrew
authors.initials: A
authors.lastname: Scribner
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D021983:Cyclophilins / Q000037:antagonists & inhibitors*; D016572:Cyclosporine / Q000737:chemistry; D008958:Models, Molecular; D014779:Virus Replication / Q000187:drug effects; D014780:Viruses / Q000187:drug effects* / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D016572:Cyclosporine; D021983:Cyclophilins
keywords: Antiviral; Cyclophilin; Cyclosporine; HIV; Hepatitis C; Immunosuppression