1. Phenoxazine nucleoside derivatives with a multiple activity against RNA and DNA viruses.
- Author
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Kozlovskaya LI, Volok VP, Shtro AA, Nikolaeva YV, Chistov AA, Matyugina ES, Belyaev ES, Jegorov AV, Snoeck R, Korshun VA, Andrei G, Osolodkin DI, Ishmukhametov AA, and Aralov AV
- Subjects
- Animals, Antiviral Agents chemical synthesis, Antiviral Agents toxicity, Cell Line, Tumor, Chlorocebus aethiops, Dogs, Humans, Madin Darby Canine Kidney Cells, Microbial Sensitivity Tests, Molecular Structure, Nucleosides chemical synthesis, Nucleosides toxicity, Oxazines chemical synthesis, Oxazines toxicity, Structure-Activity Relationship, Vero Cells, Virus Replication drug effects, Antiviral Agents pharmacology, DNA Viruses drug effects, Nucleosides pharmacology, Oxazines pharmacology, SARS-CoV-2 drug effects
- Abstract
Emerging and re-emerging viruses periodically cause outbreaks and epidemics all over the world, eventually leading to global events such as the current pandemic of the novel SARS-CoV-2 coronavirus infection COVID-19. Therefore, an urgent need for novel antivirals is crystal clear. Here we present the synthesis and evaluation of an antiviral activity of phenoxazine-based nucleoside analogs divided into three groups: (1) 8-alkoxy-substituted, (2) acyclic, and (3) carbocyclic. The antiviral activity was assessed against a structurally and phylogenetically diverse panel of RNA and DNA viruses from 25 species. Four compounds (11a-c, 12c) inhibited 4 DNA/RNA viruses with EC
50 ≤ 20 μM. Toxicity of the compounds for the cell lines used for virus cultivation was negligible in most cases. In addition, previously reported and newly synthesized phenoxazine derivatives were evaluated against SARS-CoV-2, and some of them showed promising inhibition of reproduction with EC50 values in low micromolar range, although accompanied by commensurate cytotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)- Published
- 2021
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