Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Mar 5;9(3):e89668.
doi: 10.1371/journal.pone.0089668. eCollection 2014.

Anti-enterovirus 71 effects of chrysin and its phosphate ester

Jianmin Wang  1 , Ting Zhang  1 , Jiang Du  1 , Sheng Cui  1 , Fan Yang  1 , Qi Jin  1
Affiliations

Anti-enterovirus 71 effects of chrysin and its phosphate ester

Jianmin Wang et al. PLoS One. .

Abstract

Enterovirus 71 (EV71) can cause severe disease and even lead to death in children, and an effective antiviral drug is currently unavailable. The anti-EV71 effect of chrysin (5,7-dihydroxyflavone), a natural flavonoid commonly found in many plants, was tested in this report. By using the predicting program Autodock 4.0 and an in vitro protease inhibition assay, we found that chrysin could suppress viral 3Cpro activity. Replication of viral RNA and production of viral capsid protein and the infectious virion were strongly inhibited by chrysin, without noticeable cytotoxicity. Cytopathic effects on cells were also prevented. Diisopropyl chrysin-7-yl phosphate (CPI), the phosphate ester for chrysin, was generated through a simplified Atheron-Todd reaction to achieve stronger anti-viral activity. CPI was also able to bind with and inhibit viral 3Cpro activity in vitro. As expected, CPI demonstrated more potent antiviral activity against EV71.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The inhibitory effect of CR against EV71 3Cpro in vitro.
(A) The structure for EV71 3Cpro and the chemical structure for CR. (B) Molecular docking model of CR with viral 3Cpro. (C) Protease activity of viral 3Cpro was inhibited by CR (P<0.05). Standard deviations of three independent experiments are shown.
Figure 2
Figure 2. Assessment of the cytotoxicity of CR with respect to RD cells.
1–200 µM CR exhibited no obvious inhibitory effect on the proliferation of RD cells (P>0.5). The mean value was obtained from four replicate wells; means ± SD are shown.
Figure 3
Figure 3. CR inhibits EV71 replication in RD cells.
(A), (B) CR inhibited the accumulation of EV71 RNA and capsid protein VP1 synthesis in RD cells (P<0.05). (C) EV71 plaque formation was reduced by the addition of CR (P<0.05). The experiment was performed in triplicate; bars represent means ± SD.
Figure 4
Figure 4. The effect of CR on EV71 infection.
(A) CR reduced virus-induced cytopathic effects in RD cells. (B) CR protected RD cells from EV71 infection (P<0.05). The experiment was performed in triplicate; bars represent means ± SD.
Figure 5
Figure 5. CPI inhibits EV71 3Cpro protease activity in vitro.
(A) Synthesis of CPI using a simplified Atheron-Todd reaction. (B) Molecular docking model of CPI with viral 3Cpro. (C) Protease activity for EV71 3Cpro was noticeably inhibited by CPI (P<0.05). Standard deviations of three independent experiments are shown.
Figure 6
Figure 6. Anti-EV71 effect of CPI on RD cells.
(A) 1–200 µM CPI exhibited no obvious inhibitory effect on the proliferation of RD cells (P>0.5). (B) EV71 RNA accumulation was substantially inhibited by CPI in RD cells (P<0.05). (C) CPI reduced plaque formation induced by EV71 infection (P<0.05). (D) CPI protected RD cells from EV71 infection. The mean value was obtained from three independent experiments; means ± SD are shown.
Figure 7
Figure 7. Effects of CR/CPI on established EV71 infection.
CR/CPI, added 2 or 4 hpi, substantially inhibited EV71 replication in RD cells (P<0.05). Standard deviations of three independent experiments are shown.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Liao HT, Hung KL (2001) Neurologic involvement in an outbreak of enterovirus 71 infection: a hospital-based study. Acta Paediatr Taiwan 42: 27–32. - PubMed
    1. McMinn P, Stratov I, Nagarajan L, Davis S (2001) Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. Clin Infect Dis 32: 236–242. - PubMed
    1. Li L, He Y, Yang H, Zhu J, Xu X, et al. (2005) Genetic characteristics of human enterovirus 71 and coxsackievirus A16 circulating from 1999 to 2004 in Shenzhen, People's Republic of China. J Clin Microbiol 43: 3835–3839. - PMC - PubMed
    1. Chang LY, Huang LM, Gau SS, Wu YY, Hsia SH, et al. (2007) Neurodevelopment and cognition in children after enterovirus 71 infection. N Engl J Med 356: 1226–1234. - PubMed
    1. Chu PY, Lin KH, Hwang KP, Chou LC, Wang CF, et al. (2001) Molecular epidemiology of enterovirus 71 in Taiwan. Arch Virol 146: 589–600. - PubMed

Publication types

MeSH terms

Grants and funding

The work was supported by the National Science and Technology Major Project of China, project No.2013ZX10004-601, No.2011ZX10004-001 and No.2013ZX10004-101. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.