Novel Antiviral Activity of L-Dideoxy Bicyclic Nucleoside Analogues versus Vaccinia and Measles Viruses in Vitro

作者：McGuigan Christopher; Hinsinger Karen; Farleigh Laura; Pathirana Ranjith N; Bugert Joachim J^*

来源：Journal of Medicinal Chemistry, 2013, 56(3): 1311-1322.

DOI：10.1021/jm301778x

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-C9H18-O-n-C5H11. This gave an IC50 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 TCID50 of 7.5 mu M 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.

• 出版日期2013-2-14