Inhibition of dengue virus replication by diisopropyl chrysin-7-yl phosphate

Du, Jie; Chen, Zhe; Zhang, Ting; Wang, Jianmin; Jin, Qi

doi:10.1007/s11427-016-5050-5

Cited by 7 publications

(5 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The compound at 10 µM was introduced into the virus-infected cells based on the efficacy and cytotoxicity profile. According to previous reports, viral translation is a primary target during early infection [9,12,17]. The compound is located at the perinuclear region and colocalized with a dengue protein for 1-6 h after infection (Figure 3B).…”

Section: Discussionsupporting

confidence: 75%

“…Apigenin was chosen as a flavone derivative because its existing hydroxyl group on the B-ring was suitable for a terminal alkyne modification. Although apigenin itself was a moderately potent inhibitor at the EC 50 of 10.55 ± 3.37 µM, it represented its chemical relatives like chrysins and baicaleins (Figure 1A), which were strong DENV inhibitors [9,12,17] but lacked the B-ring hydroxyl group for alkyne addition. The newly synthesized alkyne-tagged apigenin identity was verified by 1 H-NMR, and 13 C-NMR (Figures S2-S7 in Supplementary Materials).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies and reviews suggested flavonoid as a significant anti-flaviviral lead with mild toxicity in the cell-based system [7][8][9][10][11]. Quercetin [8], diisopropyl chrysin-7-yl phosphate [12], fisetin [13], glabranine and 7-O-methyl-glabranine [14] inhibited dengue RNA replication in cell-based assays. Agathisflavone, quercitrin, and isoquercitrin noncompetitively inhibited dengue virus NS2B-NS3 protease in vitro [15], whereas cyclohexenyl chalcone derivatives competitively inhibited the NS2B/NS3 protease [16].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads

et al. 2021

View full text Add to dashboard Cite

A flavonoid is a versatile core structure with various cellular, immunological, and pharmacological effects. Recently, flavones have shown anti-dengue activities by interfering with viral translation and replication. However, the molecular target is still elusive. Here we chemically modified apigenin by adding an alkyne moiety into the B-ring hydroxyl group. The alkyne serves as a chemical tag for the alkyne-azide cycloaddition reaction for subcellular visualization. The compound located at the perinuclear region at 1 and 6 h after infection. Interestingly, the compound signal started shifting to vesicle-like structures at 6 h and accumulated at 24 and 48 h after infection. Moreover, the compound treatment in dengue-infected cells showed that the compound restricted the viral protein inside the vesicles, especially at 48 h. As a result, the dengue envelope proteins spread throughout the cells. The alkyne-tagged apigenin showed a more potent efficacy at the EC50 of 2.36 ± 0.22, and 10.55 ± 3.37 µM, respectively, while the cytotoxicities were similar to the original apigenin at the CC50 of 70.34 ± 11.79, and 82.82 ± 11.68 µM, respectively. Molecular docking confirmed the apigenin binding to the previously reported target, ribosomal protein S9, at two binding sites. The network analysis, homopharma, and molecular docking revealed that the estrogen receptor 1 and viral NS1 were potential targets at the late infection stage. The interactions could attenuate dengue productivity by interfering with viral translation and suppressing the viral proteins from trafficking to the cell surface.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads

et al. 2021

View full text Add to dashboard Cite

show abstract

“…A study conducted by Du et al (2016) demonstrated the antiviral activity of a chrysin analog, a phosphate ester substituted at position 7 by a diisopropyl phosphate group, against DENV1 and DENV2. The phosphorylated analog inhibited viral protein synthesis in cells infected with DENV1 and DENV2, with IC 50 values of 18.6 and 15.1 μmol L −1 , respectively, demonstrating efficacy against the replication of these two serotypes in cell culture without detectable cytotoxicity (Du et al, 2016). Chen et al (2004) demonstrated that phosphorylated flavonoids have strong binding affinities in addition to forming noncovalent complexes with many proteins more easily than nonphosphorylated compounds (Chen et al, 2004).…”

Section: Structure: Activity Relationshipmentioning

confidence: 99%

Flavonoids as Molecules With Anti-Zika virus Activity

et al. 2021

View full text Add to dashboard Cite

Zika virus (ZIKV) is an arthropod-born virus that is mainly transmitted to humans by mosquitoes of the genus Aedes spp. Since its first isolation in 1947, only a few human cases had been described until large outbreaks occurred on Yap Island (2007), French Polynesia (2013), and Brazil (2015). Most ZIKV-infected individuals are asymptomatic or present with a self-limiting disease and nonspecific symptoms such as fever, myalgia, and headache. However, in French Polynesia and Brazil, ZIKV outbreaks led to the diagnosis of congenital malformations and microcephaly in newborns and Guillain-Barré syndrome (GBS) in adults. These new clinical presentations raised concern from public health authorities and highlighted the need for anti-Zika treatments and vaccines to control the neurological damage caused by the virus. Despite many efforts in the search for an effective treatment, neither vaccines nor antiviral drugs have become available to control ZIKV infection and/or replication. Flavonoids, a class of natural compounds that are well-known for possessing several biological properties, have shown activity against different viruses. Additionally, the use of flavonoids in some countries as food supplements indicates that these molecules are nontoxic to humans. Thus, here, we summarize knowledge on the use of flavonoids as a source of anti-ZIKV molecules and discuss the gaps and challenges in this area before these compounds can be considered for further preclinical and clinical trials.

show abstract

“…Natural compounds derived from plants have been investigated as antiviral agents against DENV. For example, quercetin, naringenin, catechin, and chrysin are flavonoids extracted from plants and were reported to have anti-dengue activity 7 – 9 . Silymarin, a plant-derived flavonoid extracted from milk thistle, was reported to be a promising antiviral candidate against chikungunya virus (CHIKV) by reducing the viral replication and down-regulation of viral proteins, nsP1, nsP3, and E2E1 10 .…”

Section: Introductionmentioning

confidence: 99%

Antiviral activity of silymarin and baicalein against dengue virus

Low

OuYong

Hassandarvish

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Dengue is an arthropod-borne viral disease that has become endemic and a global threat in many countries with no effective antiviral drug available currently. This study showed that flavonoids: silymarin and baicalein could inhibit the dengue virus in vitro and were well tolerated in Vero cells with a half-maximum cytotoxic concentration (CC50) of 749.70 µg/mL and 271.03 µg/mL, respectively. Silymarin and baicalein exerted virucidal effects against DENV-3, with a selective index (SI) of 10.87 and 21.34, respectively. Baicalein showed a better inhibition of intracellular DENV-3 progeny with a SI of 7.82 compared to silymarin. Baicalein effectively blocked DENV-3 attachment (95.59%) to the Vero cells, while silymarin prevented the viral entry (72.46%) into the cells, thus reducing viral infectivity. Both flavonoids showed promising antiviral activity against all four dengue serotypes. The in silico molecular docking showed that silymarin could bind to the viral envelope (E) protein with a binding affinity of − 8.5 kcal/mol and form hydrogen bonds with the amino acids GLN120, TRP229, ASN89, and THR223 of the E protein. Overall, this study showed that silymarin and baicalein exhibited potential anti-DENV activity and could serve as promising antiviral agents for further development against dengue infection.

show abstract

Inhibition of dengue virus replication by diisopropyl chrysin-7-yl phosphate

Cited by 7 publications

References 31 publications

Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads

Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads

Flavonoids as Molecules With Anti-Zika virus Activity

Antiviral activity of silymarin and baicalein against dengue virus

Contact Info

Product

Resources

About