title: Novel antiviral activity of l-dideoxy bicyclic nucleoside analogues versus vaccinia and measles viruses in vitro.
abstract: Dideoxy bicyclic pyrimidine nucleoside analogues (ddBCNAs) with d-chirality have previously been described by us to inhibit replication of human cytomegalovirus. We herein report for the first time that activity against vaccinia virus (VACV) was achieved using novel l-analogues. A structure-activity relationship was established: Antiviral activity versus VACV was highest with an ether side chain with an optimum of n-C(9)H(18)-O-n-C(5)H(11). This gave an IC(50) of 190 nM, a 60-fold enhancement over the FDA-approved antiviral cidofovir. Interestingly, l-ddBCNAs also inhibit wild type measles virus syncytia formation with a TCID(50) of 7.5 μM for the lead compound. We propose that l-ddBCNAs represent significant innovative antiviral candidates versus measles and poxviruses, and we suggest a mechanism of action versus one or more cellular targets that are essential for viral replication.
authors: Cardiff School of Pharmacy & Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB, U.K.
authors: Christopher
authors: C
authors: McGuigan
authors: Karen
authors: K
authors: Hinsinger
authors: Laura
authors: L
authors: Farleigh
authors: Ranjith N
authors: RN
authors: Pathirana
authors: Joachim J
authors: JJ
authors: Bugert
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008459:Measles virus / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D021241:Spectrometry, Mass, Electrospray Ionization; D014616:Vaccinia virus / Q000187:drug effects* / Q000254:growth & development; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents