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Activity of vitamin D receptor agonists against dengue virus.
Sci Rep. 2020 Jul 02; 10(1):10835.SR

Abstract

Infections with the mosquito-transmitted dengue virus (DENV) are a pressing public health problem in many parts of the world. The recently released commercial vaccine for DENV has encountered some problems, and there is still no effective drug to treat infections. Vitamin D has a well characterized role in calcium and phosphorus homeostasis, but additionally has a role in the immune response to bacterial and viral pathogens. In this study a number of fused bicyclic derivatives of 1H-pyrrolo[1,2]imidazol-1-one with vitamin D receptor (VDR) agonist activity were evaluated for possible anti-DENV activity. The results showed that five of the compounds were able to significantly inhibit DENV infection. The most effective compound, ZD-3, had an EC50 value of 7.47 μM and a selective index of 52.75. The compounds were only effective when used as a post-infection treatment and treatment significantly reduced levels of infection, virus output, DENV protein expression and genome copy number. These results suggest that these VDR agonists have the potential for future development as effective anti-DENV agents.

Authors+Show Affiliations

Institute of Molecular Biosciences, Mahidol University, Salaya, 73170, Thailand.School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 211816, Jiangsu, China.Institute of Molecular Biosciences, Mahidol University, Salaya, 73170, Thailand.School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 211816, Jiangsu, China.Institute of Molecular Biosciences, Mahidol University, Salaya, 73170, Thailand.School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 211816, Jiangsu, China.School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 211816, Jiangsu, China. gczhou@njtech.edu.cn.Institute of Molecular Biosciences, Mahidol University, Salaya, 73170, Thailand. duncan_r_smith@hotmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32616772

Citation

Jaratsittisin, Janejira, et al. "Activity of Vitamin D Receptor Agonists Against Dengue Virus." Scientific Reports, vol. 10, no. 1, 2020, p. 10835.
Jaratsittisin J, Xu B, Sornjai W, et al. Activity of vitamin D receptor agonists against dengue virus. Sci Rep. 2020;10(1):10835.
Jaratsittisin, J., Xu, B., Sornjai, W., Weng, Z., Kuadkitkan, A., Li, F., Zhou, G. C., & Smith, D. R. (2020). Activity of vitamin D receptor agonists against dengue virus. Scientific Reports, 10(1), 10835. https://doi.org/10.1038/s41598-020-67783-z
Jaratsittisin J, et al. Activity of Vitamin D Receptor Agonists Against Dengue Virus. Sci Rep. 2020 Jul 2;10(1):10835. PubMed PMID: 32616772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activity of vitamin D receptor agonists against dengue virus. AU - Jaratsittisin,Janejira, AU - Xu,Bin, AU - Sornjai,Wannapa, AU - Weng,Zhibing, AU - Kuadkitkan,Atichat, AU - Li,Feng, AU - Zhou,Guo-Chun, AU - Smith,Duncan R, Y1 - 2020/07/02/ PY - 2020/02/25/received PY - 2020/05/11/accepted PY - 2020/7/4/entrez PY - 2020/7/4/pubmed PY - 2020/7/4/medline SP - 10835 EP - 10835 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - Infections with the mosquito-transmitted dengue virus (DENV) are a pressing public health problem in many parts of the world. The recently released commercial vaccine for DENV has encountered some problems, and there is still no effective drug to treat infections. Vitamin D has a well characterized role in calcium and phosphorus homeostasis, but additionally has a role in the immune response to bacterial and viral pathogens. In this study a number of fused bicyclic derivatives of 1H-pyrrolo[1,2]imidazol-1-one with vitamin D receptor (VDR) agonist activity were evaluated for possible anti-DENV activity. The results showed that five of the compounds were able to significantly inhibit DENV infection. The most effective compound, ZD-3, had an EC50 value of 7.47 μM and a selective index of 52.75. The compounds were only effective when used as a post-infection treatment and treatment significantly reduced levels of infection, virus output, DENV protein expression and genome copy number. These results suggest that these VDR agonists have the potential for future development as effective anti-DENV agents. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/32616772/Activity_of_vitamin_D_receptor_agonists_against_dengue_virus L2 - http://dx.doi.org/10.1038/s41598-020-67783-z DB - PRIME DP - Unbound Medicine ER -
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