From the bioassay tests, 14 neuraminidase inhibitors （NIs） flavones and dihydroflavones derivatives from natural plants displayed different degree of inhibitory activities. Further- more, compounds No. 8 and 14 show...From the bioassay tests, 14 neuraminidase inhibitors （NIs） flavones and dihydroflavones derivatives from natural plants displayed different degree of inhibitory activities. Further- more, compounds No. 8 and 14 showed good inhibitory activity against influenza A virus with IC50 = 835.4 and 860.6 μg/mL. Then, to investigate interactions between NIs and neuraminidase （NA）, molecular docking was performed. Docking results indicated that Arg118, Asp151, Arg292 and Arg371 were the key residues in the active pocket of 2ht8. Main influencing factors of interactions between NIs and NA were hydrogen bond and electrostatic, then hydrophobic factor. Moreover, experimental activities of NIs were consistent with total scores of the docking. In order to understand the chemical-biological interactions governing their activities toward NA, QSAR models of 14 NIs were developed. The obtained HQSAR （hologram quantitative structure activity relationship）, PLS （partial least squares） and SRA （stepwise regression analysis） models were robust and had good exterior predictive capabilities. Moreover, squared multiple correlation coefficients （R2） and squared cross-validated correlation coefficients （Q2） of HQSAR and PLS models based on descriptors by Gaussian and Sarchitect were 0.832 and 0.721, 0.925 and 0.688, 0.892 and 0.692, respectively. R2 and SE （standard error） of SRA model based on descriptors by Gaussian were 0.922 and 0.072. Therefore, these models may be further used to design and evaluate the bioactivity of new compounds.展开更多
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.
To explore the polysaccharides from selected seaweeds of Atlantic Canada and to evaluate their potential anti-influenza virus activities, polysaccharides were isolated from several Atlantic Canadian seaweeds, includin...To explore the polysaccharides from selected seaweeds of Atlantic Canada and to evaluate their potential anti-influenza virus activities, polysaccharides were isolated from several Atlantic Canadian seaweeds, including three red algae (Polysiphonia lanosa, Furcellaria lumbricalis, and Palmaria palmata), two brown algae (Ascophyllum nodosum and Fucus vesiculosus), and one green alga (Ulva lactuca) by sequential extraction with cold water, hot water, and alkali solutions. These polysaccharides were ana-lyzed for monosaccharide composition and other general chemical properties, and they were evaluated for anti-influenza virus activities. Total sugar contents in these polysaccharides ranged from 15.4% (in U. lactuca) to 91.4% (in F. lumbricalis); sulfation level was as high as 17.6% in a polysaccharide from U. lactuca, whereas it could not be detected in an alikali-extract from P. palmaria. For polysaccharides from red seaweeds, the main sugar units were sulfated galactans (agar or carrageenan) for P. lanosa, F. lumbricalis, and xylans for P. palmata. In brown seaweeds, the polysaccharides largely contained sulfated fucans, whereas the polysaccharides in green seaweed were mainly composed of heteroglycuronans. Screening for antiviral activity against influenza A/PR/8/34 (H1N1) virus revealed that brown algal polysaccharides were particularly effective. Seaweeds from Atlantic Canada are a good source of marine polysaccharides with potential antiviral properties.展开更多
Neuraminidase （NA）, a major surface glycoprotein of influenza virus with well-defined active sites, is an ideal plat- form for the development of antiviral drugs. However, a growing number of NA mutations have drug ...Neuraminidase （NA）, a major surface glycoprotein of influenza virus with well-defined active sites, is an ideal plat- form for the development of antiviral drugs. However, a growing number of NA mutations have drug resistance to today＇s inhibitors. Numerous efforts are made to explore the resistance mechanisms through understanding the structural changes in mutated NA proteins and the associated different binding profiles of inhibitors, via x-ray, nuclear magnetic resonance, electron microscopy, and molecular dynamics methods. This review presents the architectural features of mutated NA proteins, as well as the respective inhibitor sensitivities arising from these spatial differences. Finally, we summarize the resistance mechanisms of today＇s neuraminidase inhibitors and the outlook tbr the development of novel inhibitors.展开更多
The quantitative structure-activity relationship （QSAR） of 30 acylthiourea analogues was studied by using a three-dimensional holographic vector of atomic interaction field （3D-HoVAIF） to describe their chemical s...The quantitative structure-activity relationship （QSAR） of 30 acylthiourea analogues was studied by using a three-dimensional holographic vector of atomic interaction field （3D-HoVAIF） to describe their chemical structures. The descriptors obtained were screened by stepwise multiple regression （SMR） and a partial least-squares （PLS） regression model was built. The correlation coefficient r^2 of the established model and Leave-One-Out （LOO） Cross-Validation （CV） correlation coefficient q^2 are 0.624 and 0.409, respectively. The model has favorable stability and good prediction capability, and further QSAR analysis showed that hydrophobic interaction has the most important effect on the activity of acylthiourea analogue and 3D-HoVAIF was applicable to the molecular structural characterization and biologicalactivity prediction.展开更多
Anti-influenza Chinese herbal medicines(anti-flu CHMs) have advantages in preventing and treating influenza virus infection. Despite various data on antiviral activities of some anti-flu CHMs have been reported, most ...Anti-influenza Chinese herbal medicines(anti-flu CHMs) have advantages in preventing and treating influenza virus infection. Despite various data on antiviral activities of some anti-flu CHMs have been reported, most of them could not be compared using the standard evaluation methods for antiviral activity. This situation poses an obstacle to a wide application of anti-flu CHMs. Thus, it was necessary to develop an evaluation method to estimate antiviral activities of anti-flu CHMs. In the present study, we searched for anti-flu CHMs, based on clinic usage, to select study objects from commonly-used patented anti-flu Chinese medicines. Then, a neuraminidase-based bioassay, optimized and verified by HPLC method by our research group, was adopted to detect antiviral activities of selected 26 anti-flu CHMs. Finally, eight of these herbs, including Coptidis Rhizoma, Isatidis Folium, Lonicerae Flos, Scutellaria Radix, Cyrtomium Rhizome, Houttuynia Cordata, Gardeniae Fructus, and Chrysanthemi Indici Flos, were shown to have strong antiviral activities with half maximal inhibitory concentration(IC_(50)) values being 2.02 to 6.78 mg·m L^(–1)(expressed as raw materials). In contrast, the IC_(50) value of positive control peramivir was 0.38 mg·m L^(–1). Considering the extract yields of CHMs, the active component in these herbs may have a stronger antiviral activity than peramivir, suggesting that these herbs could be further researched for active compounds. Moreover, the proposed neuraminidase-based bioassay was high-throughput and simple and could be used for evaluation and screening of anti-flu CHMs as well as for their quality control.展开更多
A new butyrolactone derivative,namely butyrolactone Ⅷ （1）,and six known butyrolactones （2-7） were separated from the ethyl acetate （EtOAc） extract of the fermentation broth of a fungus,Aspergillus terreus MXH-2...A new butyrolactone derivative,namely butyrolactone Ⅷ （1）,and six known butyrolactones （2-7） were separated from the ethyl acetate （EtOAc） extract of the fermentation broth of a fungus,Aspergillus terreus MXH-23.The chemical structures of these metabolites were identified by analyzing their nuclear magnetic resonance （NMR） and mass spectrometry （MS）.Known butyrolactone derivatives contain an α,β-unsaturated γ-lactone ring with α-hydroxyl and y-benzyl,and butyrolactone Ⅷ （1） was the first butyrolactones contains α-benzyl and γ-hydroxyl on α,β-unsaturated lactone ring.All of the butyrolactone derivatives were tested for their anti-influenza （H 1N 1） effects.Derivatives 4 and 7 showed moderate antiviral activities while the newly-identified,derivative 1,did not.展开更多
基金supported by the National Natural Science Foundation of China(No.21202110)
文摘From the bioassay tests, 14 neuraminidase inhibitors （NIs） flavones and dihydroflavones derivatives from natural plants displayed different degree of inhibitory activities. Further- more, compounds No. 8 and 14 showed good inhibitory activity against influenza A virus with IC50 = 835.4 and 860.6 μg/mL. Then, to investigate interactions between NIs and neuraminidase （NA）, molecular docking was performed. Docking results indicated that Arg118, Asp151, Arg292 and Arg371 were the key residues in the active pocket of 2ht8. Main influencing factors of interactions between NIs and NA were hydrogen bond and electrostatic, then hydrophobic factor. Moreover, experimental activities of NIs were consistent with total scores of the docking. In order to understand the chemical-biological interactions governing their activities toward NA, QSAR models of 14 NIs were developed. The obtained HQSAR （hologram quantitative structure activity relationship）, PLS （partial least squares） and SRA （stepwise regression analysis） models were robust and had good exterior predictive capabilities. Moreover, squared multiple correlation coefficients （R2） and squared cross-validated correlation coefficients （Q2） of HQSAR and PLS models based on descriptors by Gaussian and Sarchitect were 0.832 and 0.721, 0.925 and 0.688, 0.892 and 0.692, respectively. R2 and SE （standard error） of SRA model based on descriptors by Gaussian were 0.922 and 0.072. Therefore, these models may be further used to design and evaluate the bioactivity of new compounds.
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.
基金supported in part by the Program for Changjiang Scholars and Innovative Research Team in University (IRT0944)Special Fund for Marine Scientific Research in the Public Interest (201005024)the Natural Science Foundation of China (31070724), and China Scholarship Council, the Ministry of Education and National Research Council Canada-Institute for Marine Biosciences and Institute for Nutrisciences and Health
文摘To explore the polysaccharides from selected seaweeds of Atlantic Canada and to evaluate their potential anti-influenza virus activities, polysaccharides were isolated from several Atlantic Canadian seaweeds, including three red algae (Polysiphonia lanosa, Furcellaria lumbricalis, and Palmaria palmata), two brown algae (Ascophyllum nodosum and Fucus vesiculosus), and one green alga (Ulva lactuca) by sequential extraction with cold water, hot water, and alkali solutions. These polysaccharides were ana-lyzed for monosaccharide composition and other general chemical properties, and they were evaluated for anti-influenza virus activities. Total sugar contents in these polysaccharides ranged from 15.4% (in U. lactuca) to 91.4% (in F. lumbricalis); sulfation level was as high as 17.6% in a polysaccharide from U. lactuca, whereas it could not be detected in an alikali-extract from P. palmaria. For polysaccharides from red seaweeds, the main sugar units were sulfated galactans (agar or carrageenan) for P. lanosa, F. lumbricalis, and xylans for P. palmata. In brown seaweeds, the polysaccharides largely contained sulfated fucans, whereas the polysaccharides in green seaweed were mainly composed of heteroglycuronans. Screening for antiviral activity against influenza A/PR/8/34 (H1N1) virus revealed that brown algal polysaccharides were particularly effective. Seaweeds from Atlantic Canada are a good source of marine polysaccharides with potential antiviral properties.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11374237 and 11504287)Fundamental Research Funds for the Central Universities,China,China Postdoctoral Science Foundation(Grant No.2017M613147)Shaanxi Province Postdoctoral Science Foundation,China
文摘Neuraminidase （NA）, a major surface glycoprotein of influenza virus with well-defined active sites, is an ideal plat- form for the development of antiviral drugs. However, a growing number of NA mutations have drug resistance to today＇s inhibitors. Numerous efforts are made to explore the resistance mechanisms through understanding the structural changes in mutated NA proteins and the associated different binding profiles of inhibitors, via x-ray, nuclear magnetic resonance, electron microscopy, and molecular dynamics methods. This review presents the architectural features of mutated NA proteins, as well as the respective inhibitor sensitivities arising from these spatial differences. Finally, we summarize the resistance mechanisms of today＇s neuraminidase inhibitors and the outlook tbr the development of novel inhibitors.
基金supported by the National High-tech Research Program (the "863" Program, No. 2006AA02Z312)Innovative Group Program for Graduates of Chongqing University, Science and Innovation Fund (No. 200711C1A0010260)
文摘The quantitative structure-activity relationship （QSAR） of 30 acylthiourea analogues was studied by using a three-dimensional holographic vector of atomic interaction field （3D-HoVAIF） to describe their chemical structures. The descriptors obtained were screened by stepwise multiple regression （SMR） and a partial least-squares （PLS） regression model was built. The correlation coefficient r^2 of the established model and Leave-One-Out （LOO） Cross-Validation （CV） correlation coefficient q^2 are 0.624 and 0.409, respectively. The model has favorable stability and good prediction capability, and further QSAR analysis showed that hydrophobic interaction has the most important effect on the activity of acylthiourea analogue and 3D-HoVAIF was applicable to the molecular structural characterization and biologicalactivity prediction.
基金supported by the National Natural Science Foundation of China(Nos.81274026,81403126,81330090,81573676)
文摘Anti-influenza Chinese herbal medicines(anti-flu CHMs) have advantages in preventing and treating influenza virus infection. Despite various data on antiviral activities of some anti-flu CHMs have been reported, most of them could not be compared using the standard evaluation methods for antiviral activity. This situation poses an obstacle to a wide application of anti-flu CHMs. Thus, it was necessary to develop an evaluation method to estimate antiviral activities of anti-flu CHMs. In the present study, we searched for anti-flu CHMs, based on clinic usage, to select study objects from commonly-used patented anti-flu Chinese medicines. Then, a neuraminidase-based bioassay, optimized and verified by HPLC method by our research group, was adopted to detect antiviral activities of selected 26 anti-flu CHMs. Finally, eight of these herbs, including Coptidis Rhizoma, Isatidis Folium, Lonicerae Flos, Scutellaria Radix, Cyrtomium Rhizome, Houttuynia Cordata, Gardeniae Fructus, and Chrysanthemi Indici Flos, were shown to have strong antiviral activities with half maximal inhibitory concentration(IC_(50)) values being 2.02 to 6.78 mg·m L^(–1)(expressed as raw materials). In contrast, the IC_(50) value of positive control peramivir was 0.38 mg·m L^(–1). Considering the extract yields of CHMs, the active component in these herbs may have a stronger antiviral activity than peramivir, suggesting that these herbs could be further researched for active compounds. Moreover, the proposed neuraminidase-based bioassay was high-throughput and simple and could be used for evaluation and screening of anti-flu CHMs as well as for their quality control.
基金supported by National Natural Science Foundation of China (Nos.41176120 and 30973627)the National High Technology Research and Development Program of China (No.2013AA092901)+3 种基金the Program for New Century Excellent Talents in University (No.NCET12-0499)Promotive Research Fund for Excellent Young and Middle-Aged Scientists of Shandong Province (BS 2010HZ027)the Public Projects of State Oceanic Administration (No. 2010418022-3)the Program for Changjiang Scholars and Innovative Research Team in University (No.IRT0944)
文摘A new butyrolactone derivative,namely butyrolactone Ⅷ （1）,and six known butyrolactones （2-7） were separated from the ethyl acetate （EtOAc） extract of the fermentation broth of a fungus,Aspergillus terreus MXH-23.The chemical structures of these metabolites were identified by analyzing their nuclear magnetic resonance （NMR） and mass spectrometry （MS）.Known butyrolactone derivatives contain an α,β-unsaturated γ-lactone ring with α-hydroxyl and y-benzyl,and butyrolactone Ⅷ （1） was the first butyrolactones contains α-benzyl and γ-hydroxyl on α,β-unsaturated lactone ring.All of the butyrolactone derivatives were tested for their anti-influenza （H 1N 1） effects.Derivatives 4 and 7 showed moderate antiviral activities while the newly-identified,derivative 1,did not.
