OBJECTIVE Sheng Jiang San(SJS),a multi-herb formulation,is used in treating high fever,thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza in modern.However,there is no evidenceba...OBJECTIVE Sheng Jiang San(SJS),a multi-herb formulation,is used in treating high fever,thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza in modern.However,there is no evidencebased investigation and mechanism research to support SJS′s anti-influenza efficacy.This study aims to investigate the anti-influenza effect of SJS and its possible mechanisms.METHODS In this study,we examined the inhibitory effect of SJS against different influenza viruses on Madin-Darby canine kidney cells.Influenza virus infected BALB/c mice were employed as in vivo model to evaluate the efficacy.Mice challenged with A/PR/8/34(H1N1)were orally administrated SJS 1 g·kg^-1 daily for seven days and monitored for 14 d.The survival rate,body mass changes,lung index,lung viral load,histopathologic changes and immune-regulation of the mice were measured.The underlying anti-influenza virus mechanisms were studied by a series of biological assays in vitro to determine if hemagglutinin,ribonucleoprotein complex or nerauminidase were targets of SJS.RESULTS SJS exerted a broad spectrum of inhibitory effects on multiple influenza strains in a dose-dependent manner.And IC50 of SJS against A/WSN/33(H1N1)was lower than 35 mg·L^-1.SJS also protected 50%of mice from influenza virus PR8 infection.The lung index and the lung viral load of SJS treated mice were signifi⁃cantly decrease compared with untreated mice.SJS 2 g·L^-1 inhibited 80%of neuraminidase enzymatic activity.SJS also up-regulated TNF-αand IFN-αand down-regulated IL-2 of influenza virus induced mice.CONCLUSION SJS is a useful formulation for treating influenza virus infection.展开更多
A series of ethyl 6-bromo-5-hydroxyindole-3-carboxylate derivatives were synthesized and their in vitro anti-influenza virus activity was evaluated. All the compounds were characterized by 1H NMR and MS.
Virus nucleoprotein (NP) is an emerging target for drug development for Influenza. We designed benzamide derivatives as new inhibitors of NP that demonstrate good potency in blocking influenza A. Screening revealed th...Virus nucleoprotein (NP) is an emerging target for drug development for Influenza. We designed benzamide derivatives as new inhibitors of NP that demonstrate good potency in blocking influenza A. Screening revealed that compound 39 was the most potent molecule in the series, exhibiting IC<sub>50</sub> values of 0.46 and 0.27 μM in blocking the replication of H3N2 (A/HK/8/68) and (A/WSN/33) influenza A viral strains. The observed inhibition of viral replication correlated well with cytopathic protection. Furthermore, based on computational analysis and fluorescence microscopy, it was determined that compound 39 inhibited nuclear accumulation by targeting influenza A viral nucleoproteins. Finally, the rodent pharmacokinetic profile of compound 32 displayed half-life of greater than 4 hours and bioavailability greater than 20%, suggesting this class of molecules had drug-like properties.展开更多
Influenza virus infection is a global public health issue.The effectiveness of antiviral agents for influenza has been limited by the emergence of drugresistant virus strains.Therefore,there is an urgent need to ident...Influenza virus infection is a global public health issue.The effectiveness of antiviral agents for influenza has been limited by the emergence of drugresistant virus strains.Therefore,there is an urgent need to identify novel antiviral therapies.Our previous studies have found that Cryptoporus volvatus extract could potently inhibit influenza virus replication in vitro and in vivo.However,the effective component of Cryptoporus volvatus which mediated the antiviral activity hasn′t been identified.Here,we identified a novel anti-influenza molecule,cryptoporic acid E(CAE),from Cryptoporus volvatus.Our results showed that CAE had broad-spectrum anti-influenza activity against 2009 pandemic strain A/Beijing/07/2009(H1N1/09),seasonal strain A/Jiangxi/262/05(H3N2),mouse adapted strains A/WSN/33(H1N1)and A/PR8/34(H1N1).We further investigated the mode of CAE action,and found that CAE directlyattenuated influenza virus infectivity.Time-course-analysis indicated that CAE exerted its inhibition mainly at middle stage of the replication cycle of influenza virus.Subsequently,we confirmed that CAE blocked virus RNA replication and transcription in MDCK cells and CAE repressed influenza virus RNA polymerase activity.In addition,we found that CAE impaired influenza virus infectivity by directly targeting virus particles.Our data suggest that CAE is a major effective component of Cryptoporus volvatus and might be a potential candidate for the development of a new anti-influenza virus therapy.展开更多
文摘OBJECTIVE Sheng Jiang San(SJS),a multi-herb formulation,is used in treating high fever,thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza in modern.However,there is no evidencebased investigation and mechanism research to support SJS′s anti-influenza efficacy.This study aims to investigate the anti-influenza effect of SJS and its possible mechanisms.METHODS In this study,we examined the inhibitory effect of SJS against different influenza viruses on Madin-Darby canine kidney cells.Influenza virus infected BALB/c mice were employed as in vivo model to evaluate the efficacy.Mice challenged with A/PR/8/34(H1N1)were orally administrated SJS 1 g·kg^-1 daily for seven days and monitored for 14 d.The survival rate,body mass changes,lung index,lung viral load,histopathologic changes and immune-regulation of the mice were measured.The underlying anti-influenza virus mechanisms were studied by a series of biological assays in vitro to determine if hemagglutinin,ribonucleoprotein complex or nerauminidase were targets of SJS.RESULTS SJS exerted a broad spectrum of inhibitory effects on multiple influenza strains in a dose-dependent manner.And IC50 of SJS against A/WSN/33(H1N1)was lower than 35 mg·L^-1.SJS also protected 50%of mice from influenza virus PR8 infection.The lung index and the lung viral load of SJS treated mice were signifi⁃cantly decrease compared with untreated mice.SJS 2 g·L^-1 inhibited 80%of neuraminidase enzymatic activity.SJS also up-regulated TNF-αand IFN-αand down-regulated IL-2 of influenza virus induced mice.CONCLUSION SJS is a useful formulation for treating influenza virus infection.
文摘A series of ethyl 6-bromo-5-hydroxyindole-3-carboxylate derivatives were synthesized and their in vitro anti-influenza virus activity was evaluated. All the compounds were characterized by 1H NMR and MS.
文摘Virus nucleoprotein (NP) is an emerging target for drug development for Influenza. We designed benzamide derivatives as new inhibitors of NP that demonstrate good potency in blocking influenza A. Screening revealed that compound 39 was the most potent molecule in the series, exhibiting IC<sub>50</sub> values of 0.46 and 0.27 μM in blocking the replication of H3N2 (A/HK/8/68) and (A/WSN/33) influenza A viral strains. The observed inhibition of viral replication correlated well with cytopathic protection. Furthermore, based on computational analysis and fluorescence microscopy, it was determined that compound 39 inhibited nuclear accumulation by targeting influenza A viral nucleoproteins. Finally, the rodent pharmacokinetic profile of compound 32 displayed half-life of greater than 4 hours and bioavailability greater than 20%, suggesting this class of molecules had drug-like properties.
基金The project supported by Young Scientist Funding from Beijing Natural Science Foundation(7154225)by Innovative Research Team in IMPLAD
文摘Influenza virus infection is a global public health issue.The effectiveness of antiviral agents for influenza has been limited by the emergence of drugresistant virus strains.Therefore,there is an urgent need to identify novel antiviral therapies.Our previous studies have found that Cryptoporus volvatus extract could potently inhibit influenza virus replication in vitro and in vivo.However,the effective component of Cryptoporus volvatus which mediated the antiviral activity hasn′t been identified.Here,we identified a novel anti-influenza molecule,cryptoporic acid E(CAE),from Cryptoporus volvatus.Our results showed that CAE had broad-spectrum anti-influenza activity against 2009 pandemic strain A/Beijing/07/2009(H1N1/09),seasonal strain A/Jiangxi/262/05(H3N2),mouse adapted strains A/WSN/33(H1N1)and A/PR8/34(H1N1).We further investigated the mode of CAE action,and found that CAE directlyattenuated influenza virus infectivity.Time-course-analysis indicated that CAE exerted its inhibition mainly at middle stage of the replication cycle of influenza virus.Subsequently,we confirmed that CAE blocked virus RNA replication and transcription in MDCK cells and CAE repressed influenza virus RNA polymerase activity.In addition,we found that CAE impaired influenza virus infectivity by directly targeting virus particles.Our data suggest that CAE is a major effective component of Cryptoporus volvatus and might be a potential candidate for the development of a new anti-influenza virus therapy.
