English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Bicyclic pyrimidine nucleoside analogues (BCNAs) represent highly potent and selective inhibitors of varicella-zoster virus (VZV) replication in cell culture. The compounds inhibit a variety of clinical VZV strains, in the higher picomolar range, whilst being non-toxic at micromolar concentrations. The compounds do not inhibit the closely related simian varicella virus or any other viruses, including herpes simplex virus type 1 (HSV-1), HSV-2 and cytomegalovirus. The BCNAs owe at least part of their antiviral selectivity to a specific activation/phosphorylation by the VZV-encoded thymidine kinase (TK) and associated thymidylate kinase (dTMP-K) activity, while being not recognized by the closely related HSV-1-encoded TK/dTMP-K enzyme. In addition, the 5'-monophosphates of BCNAs are neither a substrate nor an inhibitor of the cellular dTMP-K, and are not subject of back-conversion to the corresponding nucleosides by 5'-deoxynucleotidases. In contrast to the anti-HSV-1/VZV drug (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), the BCNAs are not catabolized by human (erythrocyte) or bacterial (Escherichia coli) thymidine phosphorylase to release the free bicyclic pyrimidine base. Also, unlike BVU (the free base of BVDU), the BCNA bases do not inhibit dihydropyrimidine dehydrogenase. Consequently, the catabolism of the anticancer drug 5-fluorouracil (5-FU) is not influenced by the BCNA base in cell-free enzyme assays or in mice that were exposed to combinations of 5-FU with BCNAs or their free base. BCNAs have a good oral bioavailability and, owing to their highly lipophilic nature, are assumed to be able to cross the blood-brain barrier efficiently. Given the above-mentioned favourable properties, BCNAs may represent a promising novel class of highly selective anti-VZV drugs that should be further pursued for clinical application.

Bicyclic pyrimidine nucleoside analogues (BCNAs) as highly selective and potent inhibitors of varicella-zoster virus replication