2. Academic Validation
  3. Anti-HCV and Zika activities of ribavirin C-nucleosides analogues

Anti-HCV and Zika activities of ribavirin C-nucleosides analogues

  • Bioorg Med Chem. 2022 Aug 15:68:116858. doi: 10.1016/j.bmc.2022.116858.
Simon Gonzalez 1,  Gabriela Brzuska 2,  Abdelhakim Ouarti 1,  Florian Gallier 1,  Carmen Solarte 1,  Angélique Ferry 1,  Jacques Uziel 1,  Ewelina Krol 3,  Nadège Lubin-Germain 4
Affiliations

Affiliations

  • 1 CY Cergy Paris Université, CNRS, BioCIS, 95000 Cergy Pontoise, France; Université Paris-Saclay, CNRS, BioCIS, 92290 Châtenay-Malabry, France.
  • 2 Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.
  • 3 Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland. Electronic address: [email protected].
  • 4 CY Cergy Paris Université, CNRS, BioCIS, 95000 Cergy Pontoise, France; Université Paris-Saclay, CNRS, BioCIS, 92290 Châtenay-Malabry, France. Electronic address: [email protected].
PMID: 35661850 DOI: 10.1016/j.bmc.2022.116858
Abstract

Ribavirin is an unnatural nucleoside exhibiting broad spectrum of Antiviral and antitumor activities, still very widely studied particularly in a repositioning approach. C-triazolyl nucleoside analogues of ribavirin have been synthesized, as well as prodrugs and glycosylated or peptide conjugates to allow a better activity by vectorization into the liver or by facilitating uptake into the cells. The Antiviral properties of all synthesized compounds have been evaluated in vitro against two important human viral pathogens belonging to the Flaviviridae family: hepatitis C virus (HCV) and Zika virus (ZIKV). There are no therapeutic options for Zika virus, whereas those available for HCV can be still improved. Our results indicated that compound 2 carrying an N-hydroxy carboxamide function exhibits the most inhibitory activities against both viruses. This compound moderately inhibited the propagation of HCV with an IC50 value of 49.1 μM and Zika virus with an IC50 of 33.2 μM comparable to ribavirin in the Vero cell line. The results suggest that compound 2 and its new derivatives may be candidates for further development of new anti-HCV and anti-ZIKV Antiviral drugs.

Keywords

Antiviral activities; C-nucleoside; Dengue; Hepatitis C; Ribavirin; Zika virus.

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