Activity of vitamin D receptor agonists against dengue virus

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.

Vitamin D and COVID‐19: A review on the role of vitamin D in preventing and reducing the severity of COVID‐19 infection

“…Also, treatment of Dengue‐infected monocytic U937 cells with vitamin D resulted in a significant reduction in the number of infected cells; vitamin D also lowered the levels of proinflammatory cytokines 52 . In a separate study, VDR agonists were found to have antiviral activities 53 . It has also been reported that vitamin D has a preventive effect on SARS‐CoV‐2 viral infection, which causes immune activation and systemic hyperinflammation 54 …”

The vitamin D receptor agonist EB1089 can exert its antiviral activity independently of the vitamin D receptor

“…In a previous study, we established that a different, chemically synthesized vitamin D receptor agonist, ZD-6, had antiviral activity against ZIKV [ 26 ], both that study and this study were undertaken in HEK293T/17 cells. To investigate whether EB1089 has antiviral activity in a more biologically relevant system, the effect of EB1089 on ZIKV infected neural progenitor cells, which are one of the primary targets of this virus infection [ 50 ], was determined.…”

“…VDR-mediated gene expression analysis was undertaken essentially as described previously [ 26 ]. Briefly, cells were lysed and RNA was extracted using Trizol (Thermo Fisher Scientific Inc., Waltham, MA) according to the manufacturer’s recommendations.…”

Importance of functional nutrition components on new Coronavirus disease (COVID-19) and other viral communicable diseases

“…According to various studies, calcitriol an active form of vitamin D is activated by ultraviolet radiations, it was determined that the calcitriol lead a rise in the production of antiviral peptidase (Gombart et al, 2020). In another study (Jaratsittisin et al, 2020), it was suggested that vitamin D receptor agonists (VDR) was an effective anti-DENV agents. In different studies, it was shown that vitamin D is significantly associated with virus replication in chronic HBV infection, and that insufficient vitamin D levels most likely fail to suppress hepatitis B Virus (HBV) replication and contribute to poor clinical courses (Hoan et al, 2016).…”