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Medicinal Chemistry Research

, Volume 26, Issue 7, pp 1382–1387 | Cite as

Nucleoside analogs as potential antiviral agents for dengue virus infections

  • Kiroshika Pillai Veel Pilay
  • Malina Jasamai
  • Ravindran Thayan
  • Jacinta Santhanam
  • Sharifah Syed Hassan
  • Wei Boon Yap
Original Research
  • 141 Downloads

Abstract

Dengue virus is the causative agent of dengue fever and also the most prevalent mosquito borne viral pathogen. Up until now, treatments for dengue fever rely mainly on intensive supportive therapies. This study aimed to investigate in vitro antiviral activities of selected nucleoside analogs. These drugs were selected based on their good interactions with dengue virus replicating enzyme in a computer modeling study. The cytotoxicity of the nucleoside analogs in green monkey kidney cell line (VERO) was verified using the MTT [(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Among the drugs tested, adenovir dipivoxil exhibited toxicity to cells with only 20–40% cell viability at drug concentrations above 100 µM. Therefore, adenovir dipivoxil was omitted from the plaque reduction assay. The nucleoside analogs were further evaluated in a plaque reduction assay and ribavirin was used as a positive control. VERO cells were infected with dengue virus-2 at a multiplicity of infection of 0.4 and then treated with different concentrations of nucleoside analogs. Virus plaques were observed and counted after 7 days of incubation. The results showed that valganciclovir and stavudine inhibited dengue virus-2 replication by 6–21%. These nucleoside analogs may, therefore, have the potential to be used in treating dengue infections.

Keywords

Dengue virus Nucleoside analogs MTT assay Plaque assay Antiviral drug 

Notes

Acknowledgements

This work is supported by FRGS (FRGS/1/2012/SKK02/UKM/02/3) and DLP-2013-035 grants.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Kiroshika Pillai Veel Pilay
    • 1
  • Malina Jasamai
    • 2
  • Ravindran Thayan
    • 3
  • Jacinta Santhanam
    • 1
  • Sharifah Syed Hassan
    • 4
  • Wei Boon Yap
    • 1
  1. 1.Programme of Biomedical Sciences, School of Diagnostic and Applied Health Sciences, Faculty of Health SciencesUniversiti Kebangsaan MalaysiaKuala LumpurMalaysia
  2. 2.Drugs and Herbal Research Center, Faculty of PharmacyUniversiti Kebangsaan MalaysiaKuala LumpurMalaysia
  3. 3.Virology UnitInstitute for Medical ResearchKuala LumpurMalaysia
  4. 4.Jeffrey Cheah School of Medicine and Health Sciences Monash University MalaysiaBandar SunwayMalaysia

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