Ginsenoside Rb1 is an immune-stimulatory agent with antiviral activity against enterovirus 71

Influenza viruses cause respiratory infections in humans and animals, which have high morbidity and mortality rates. Although several drugs that inhibit viral neuraminidase are used to treat influenza infections, the emergence of resistant viruses necessitates the urgent development of new antiviral drugs. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that exhibits antiviral activity against enterovirus 71 (EV71) by inhibiting viral 3C protease activity. In this study, we evaluated the antiviral activity of chrysin against influenza A/Puerto Rico/8/34 (A/PR/8). Chrysin significantly inhibited A/PR/8-mediated cell death and the replication of A/PR/8 at concentrations up to 2 mM. Viral hemagglutinin expression was also markedly decreased by the chrysin treatment in A/PR/8-infected cells. Through the time course experiment and time-of-addition assay, we found that chrysin inhibited viral infection at the early stages of the replication cycle. Additionally, the nucleoprotein expression of A/PR/8 in A549 cells was reduced upon treatment with chrysin. Regarding the mechanism of action, we found that chrysin inhibited autophagy activation by increasing the phosphorylation of mammalian target of rapamycin (mTOR). We also confirmed a decrease in LC3B expression and LC3-positive puncta levels in A/PR/8-infected cells. These results suggest that chrysin exhibits antiviral activity by activating mTOR and inhibiting autophagy to inhibit the replication of A/PR/8 in the early stages of infection.

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Synthesis and Broad Antiviral Activity of Novel 2-aryl-isoindolin-1-ones towards Diverse Enterovirus A71 Clinical Isolates

Molecules ◽

10.3390/molecules24050985 ◽

2019 ◽

Vol 24 (5) ◽

pp. 985 ◽

Cited By ~ 1

Author(s):

Yixuan Wang ◽

Huiqiang Wang ◽

Xinbei Jiang ◽

Zhi Jiang ◽

Tingting Guo ◽

...

Keyword(s):

Antiviral Activity ◽

Enterovirus 71 ◽

Foot And Mouth Disease ◽

Viral Disease ◽

Clinical Isolates ◽

Dependent Manner ◽

Potent Antiviral Activity ◽

Sar Studies ◽

Enterovirus A71

Enterovirus 71 (EV-A71) is the main causative pathogen of childhood hand, foot and mouth disease. Effective medicine is currently unavailable for the treatment of this viral disease. Using the fragment-hopping strategy, a series of 2-aryl-isoindolin-1-one compounds were designed, synthesized and investigated for their in vitro antiviral activity towards multiple EV-A71 clinical isolates (H, BrCr, Shenzhen98, Jiangsu52) in Vero cell culture in this study. The structure–activity relationship (SAR) studies identified 2-phenyl-isoindolin-1-ones as a new potent chemotype with potent antiviral activity against EV-A71. Ten out of the 24 tested compounds showed significant antiviral activity (EC50 < 10 µM) towards four EV-A71 strains. Compounds A3 and A4 exhibited broad and potent antiviral activity with the 50% effective concentration (EC50) values in the range of 1.23–1.76 μM. Moreover, the selectivity indices of A3 and A4 were significantly higher than those of the reference compound, pirodavir. The western blotting experiment indicated that the viral VP1 was significantly decreased at both the protein and RNA level in a dose-dependent manner following treatment with compound A3. Moreover, compound A3 inhibited the viral replication by acting on the virus entry stage. In summary, this study led to the discovery of 2-aryl-isoindolin-1-ones as a promising scaffold with potent anti-EV-A71 activities, which deserves further in-depth studies.

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Aloe-emodin is an interferon-inducing agent with antiviral activity against Japanese encephalitis virus and enterovirus 71

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2008.04.018 ◽

2008 ◽

Vol 32 (4) ◽

pp. 355-359 ◽

Cited By ~ 60

Author(s):

Cheng-Wen Lin ◽

Chia-Fang Wu ◽

Nai-Wan Hsiao ◽

Ching-Yao Chang ◽

Shih-Wein Li ◽

...

Keyword(s):

Antiviral Activity ◽

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Enterovirus 71 ◽

Encephalitis Virus ◽

Aloe Emodin

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Antiviral activity of a polysaccharide from Laminaria japonica against enterovirus 71

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2017.09.117 ◽

2017 ◽

Vol 96 ◽

pp. 256-262 ◽

Cited By ~ 8

Author(s):

Yingying Yue ◽

Zhihui Li ◽

Peng Li ◽

Nannan Song ◽

Bingqing Li ◽

...

Keyword(s):

Antiviral Activity ◽

Enterovirus 71 ◽

Laminaria Japonica

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Chebulagic Acid, a Hydrolyzable Tannin, Exhibited Antiviral Activity in Vitro and in Vivo against Human Enterovirus 71

International Journal of Molecular Sciences ◽

10.3390/ijms14059618 ◽

2013 ◽

Vol 14 (5) ◽

pp. 9618-9627 ◽

Cited By ~ 23

Author(s):

Yajun Yang ◽

Jinghui Xiu ◽

Jiangning Liu ◽

Li Zhang ◽

Xiaoying Li ◽

...

Keyword(s):

Antiviral Activity ◽

Enterovirus 71 ◽

Human Enterovirus ◽

Hydrolyzable Tannin ◽

Human Enterovirus 71 ◽

Chebulagic Acid

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Antiviral Effects ofSalvia miltiorrhiza(Danshen) Against Enterovirus 71

The American Journal of Chinese Medicine ◽

10.1142/s0192415x07004709 ◽

2007 ◽

Vol 35 (01) ◽

pp. 153-168 ◽

Cited By ~ 31

Author(s):

Bin-Wen Wu ◽

Tai-Long Pan ◽

Yann-Lii Leu ◽

Yu-Kaung Chang ◽

Pei-Ju Tai ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Entry ◽

Cytopathic Effect ◽

Salvia Miltiorrhiza ◽

Enterovirus 71 ◽

Vero Cells ◽

The Other ◽

Antiviral Effects ◽

Antiviral Activities ◽

Infected Cells

In this study, the antiviral activities of seven different extracts of Salvia miltiorrhiza (danshen) were determined. The first two extracts, SA1 and SA2, isolated at room temperature by ethyl acetate and water extraction, respectively, neutralized the enterovirus 71-induced cytopathic effect in Vero, rhabdomyosarcoma and MRC-5 cells. The other five crude extracts, extracted with warm water (60–70°C) or organic solvents, did not have any protective activity. The 50% inhibitory concentrations for neutralizing the enterovirus 71-induced cytopathic effect were 0.742 ± 0.042 mg/ml for SA1 and 0.585 ± 0.018 mg/ml for SA2 in Vero cells. No antiviral activity was observed in the other viruses tested. Antiviral activity was more efficient in cultures treated with SA1 or SA2 during viral infection compared to the cultures treated before or after infection, suggesting that these danshen extracts could interfere with viral entry. SA1 and SA2 were able to inhibit viral RNA synthesis in the infected cells and to abate the apoptotic process in enterovirus 71-infected Vero cells. We conclude that danshen extracts possess antiviral activity and have potential for the development as an anti-enterovirus 71 agent.

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