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Nucleoside analogs as potential antiviral agents for dengue virus infections

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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.

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Acknowledgements

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

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Authors and Affiliations

  1. Programme of Biomedical Sciences, School of Diagnostic and Applied Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 50300, Wilayah Persekutuan Kuala Lumpur, Malaysia

    Kiroshika Pillai Veel Pilay, Jacinta Santhanam & Wei Boon Yap

  2. Drugs and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abd. Aziz, Kuala Lumpur, 50300, Wilayah Persekutuan Kuala Lumpur, Malaysia

    Malina Jasamai

  3. Virology Unit, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, 50300, Wilayah Persekutuan Kuala Lumpur, Malaysia

    Ravindran Thayan

  4. Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500, Selangor, Darul Ehsan, Malaysia

    Sharifah Syed Hassan

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  1. Kiroshika Pillai Veel Pilay
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  2. Malina Jasamai
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  3. Ravindran Thayan
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  4. Jacinta Santhanam
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  5. Sharifah Syed Hassan
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  6. Wei Boon Yap
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Correspondence to Wei Boon Yap.

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Veel Pilay, K., Jasamai, M., Thayan, R. et al. Nucleoside analogs as potential antiviral agents for dengue virus infections. Med Chem Res 26, 1382–1387 (2017). https://doi.org/10.1007/s00044-017-1863-4

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  • DOI: https://doi.org/10.1007/s00044-017-1863-4

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