Nucleoside analogs as potential antiviral agents for dengue virus infections
- 124 Downloads
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.
KeywordsDengue virus Nucleoside analogs MTT assay Plaque assay Antiviral drug
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.
- Chen YL, Yin Z, Duraiswamy J, Schul W, Lim CC, Liu P, Xu HY, Qing M, Yip A, Wang G, Chan WL, Tan HP, Lo M, Liung S, Kondreddi RR, Rao R, Gu H, He H, Keller TH, Shi PY (2010) Inhibition of dengue virus RNA synthesis by an adenosine nucleoside. Antimicrob Agents Chemother 54:2932–2939CrossRefPubMedPubMedCentralGoogle Scholar
- Haggard PG, Kewn S, Barry MG, Khoo SH, Back DJ (1997) Effects of drug on 2′,3′-dideoxy-2′,3′-didehydrothymidine phosphorylation in vitro. Antimicrob Agents Chemother 41:1231–1236Google Scholar
- Simmons JS, St. John JH, Reynolds FHK (1931) Experimental studies of dengue. Philipp J Sci 44:1–251Google Scholar
- World Health Organisation (2016) Dengue situation update 496. http://Reliefweb.int/report/malaysia/dengue-situation-update-496-26-july-2016 Assessed 10 Oct 2016
- Yin Z, Chen YL, Schul W, Wang QY, Gu F, Duraiswamy J, Kondreddi RR, Niyomrattanakit P, Lakshminarayana SB, Goh A, Xu HY, Liu W, Liu B, Lim JY, Ng CY, Qing M, Lim CC, Yip A, Wang G, Chan WL, Tan HP, Lin K, Zhang B, Zou G, Bernard KA, Garrett C, Beltz K, Dong M, Weaver M, He H, Pichota A, Dartois V, Keller TH, Shi PY (2009) An adenosine nucleoside inhibitor of dengue virus. Proc Natl Acad Sci 106:20435–20439CrossRefPubMedPubMedCentralGoogle Scholar