Novel antiviral activity of l-dideoxy bicyclic nucleoside analogues versus vaccinia and measles viruses in vitro

McGuigan, Christopher ORCID: https://orcid.org/0000-0001-8409-710X, Hinsinger, Karen, Farleigh, Laura, Pathirana, Ranjith and Bugert, Joachim J. ORCID: https://orcid.org/0000-0002-0556-3211 2013. Novel antiviral activity of l-dideoxy bicyclic nucleoside analogues versus vaccinia and measles viruses in vitro. Journal of Medicinal Chemistry 56 (3) , pp. 1311-1322. 10.1021/jm301778x

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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-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 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Pharmacy Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > RM Therapeutics. Pharmacology
Publisher:	American Chemical Society
ISSN:	0022-2623
Last Modified:	09 Aug 2024 13:51
URI:	https://orca.cardiff.ac.uk/id/eprint/43409

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