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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.

Antipyretic and toxin-eliminating traditional Chinese herbs are believed to possess antiviral activity. In this study, we screened extracts of 22 herbs for activity against enterovirus 71 (EV71). We found that only extracts of Houttuynia cordata Thunb. could neutralize EV71-induced cytopathic effects in Vero cells. The 50% inhibitory concentration of H. cordata extract for EV71 was 125.92 ± 27.84 μg/ml. Antiviral screening of herb extracts was also conducted on 3 genotypes of EV71, coxsackievirus A16 and echovirus 9. H. cordata extract had the highest activity against genotype A of EV71. A plaque reduction assay showed that H. cordata extract significantly reduced plaque formation. Viral protein expression, viral RNA synthesis and virus-induced caspase 3 activation were inhibited in the presence of H. cordata extract, suggesting that it affected apoptotic processes in EV71-infected Vero cells by inhibiting viral replication. The antiviral activity of H. cordata extract was greater in cells pretreated with extract than those treated after infection. We conclude that H. cordata extract has antiviral activity, and it offers a potential to develop a new anti-EV71 agent.

Enterovirus 71 (EV71) and coxsackievirus B3 (CVB3) have resulted in severe pathogenesis caused by the host's immune response, including the cytokine cascade. Paris polyphylla Smith is a folk medicinal plant in Asia traditionally prescribed for the reduction of pain and elimination of poisoning. In this study, we investigated the anti-EV71 and CVB3 activity of P. polyphylla Smith as well as its immune modulation. The IC₅₀ for the P. polyphylla Smith 95% ethanol extract against EV71 and CVB3 were 12.5–23% and 99–156% of that of ribavirin, a positive control. Prevention of viral infection, viral inactivation, and anti-viral replication effects against both EV71 and CVB3 were demonstrated by the extract, the anti-viral replication effect being dominant. The extract significantly increased IL-6 production in both EV71- and CVB3-infected cells. A high correlation was possibly demonstrated between the high amounts of IL-6 induction in the EV71 and CVB3-infected cells and the anti-viral replication activity of the extract. In conclusion, good anti-EV71 and CVB3 activity was observed in the P. polyphylla Smith 95% ethanol extract. The high amounts of IL-6 induction in the virus-infected cells played a key role in the anti-viral activity of the extract.

The enterovirus 71 infection is associated with severe neurological disease in several clinical researches; however, the detailed gene network mechanisms of enterovirus 71-infected cells remain unclear at present. We present a new approach integrating microarray expression data, KEGG database, gene ontology (GO), and OMIM information for efficiently deciphering pathways of enterovirus 71-infected cells. This approach includes the following steps: (1) profiling the significant gene-gene interaction through pathway database, (2) utilizing Fisher's exact test to analyze pathway information and to rank the first ten significant pathways, (3) annotating functions of genes in the pathways through gene ontology, (4) investigating related genes and perhaps concern diseases by referring to OMIM information. Our findings illustrate at least three possible pathways in enterovirus 71-infected human neural SF268 cells: Jak-STAT signaling: cell cycle and apoptosis. Furthermore, we show that some genes are associated with neural development and neural apoptosis, such as c-Myc, BAX, NGF, and CPP32. These would be useful for profiling disease mechanisms and host response to virus in future research.

In 1998, the enterovirus (EV) infections outbreak in Taiwan caused 78 fatalities. Since then, EV infections have continuously posed a threat to the public. Among the 64 serotypes of enteroviruses known to infect human, the enterovirus 71(EV71) is suspected to be the major cause for severe cases. In this study, we estimate the recombination point of enterovirus 71 vp1 by using the method of Likelihood Analysis of Recombination in DNA. The datasets of enterovirus 71 DNA sequences are available in GenBank. After careful cross validation, eight candidate sequences are chosen to advance analysis, including 2734TAI98, TW227298, 1423SIN98 and other five DNA sequences as well. Then, the construction of the phylogeny trees (neighbor-joining trees will be used in this paper) would support for recombination in EV71 virus. In these two methods, the breakpoint was found to be in similar position, demonstrating that a single recombination event occurred prior to the divergence of these two strains.