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| 1 | Recent advances in the anti-HCV mechanisms of interferon显示文摘Interferon(IFN)in combination with ribavirin has been the standard of care(SOC)for chronic hepatitis C for the past few decades.Although the current SOC lacks the desired efficacy,and 4 new direct-acting antiviral agents have been recently approved,interferons are still likely to remain the cornerstone of therapy for some time.Moreover,as an important cytokine system of innate immunity,host interferon signaling provides a powerful antiviral response.Nevertheless,the mechanisms by which HCV infection controls interferon production,and how interferons,in turn,trigger anti-HCV activities as well as control the outcome of HCV infection remain to be clarified.In this report,we review current progress in understanding the mechanisms of IFN against HCV,and also summarize the knowledge of induction of interferon signaling by HCV infection. | Menghao Huang Jian-Dong Jiang Zonggen Peng | 2014 | Acta Pharmaceutica Sinica B2014,4,4: | 4 |
| 2 | Synthesis and biological evaluation of sophocarpinic acid derivatives as anti-HCV agents显示文摘Chronic hepatitis C virus(HCV)infection has become a major public health burden worldwide.Twenty-two sophocarpinic acid or matrine derivatives were synthesized and their anti-HCV activities were evaluated in vitro.The structure-activity analysis revealed that(i)sophocarpinic acids with a D-seco 3-ring structure scaffold were more favorable than matrines with a 4-ring scaffold;(ii)the introduction of an electron-withdrawing group on the phenyl ring in 12-N-benzenesulfonylΔβγsophocarpinic acids was beneficial for the antiviral activity against HCV.Among them,compounds 9h and 9j exhibited the most potent inhibitory activities on HCV replication with selectivity indies of 70.3 and 30.9,respectively.Therefore,both were selected as antiviral candidates for further investigation. | Yinghong Li Zonggen Peng Limei Gao Danqing Song | 2014 | Acta Pharmaceutica Sinica B2014,4,4: | 4 |
| 3 | Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication显示文摘Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication. | Meng-Hao Huang Hu Li Rong Xue Jianrui Li Lihua Wang Junjun Cheng Zhouyi Wu Wenjing Li Jinhua Chen Xiaoqin Lv Qiang Li Pei Lan Limin Zhao Yongfeng Yang Zonggen Peng Jiandong Jiang | 2019 | Acta Pharmaceutica Sinica B2019,9,4: | 3 |
| 4 | Synthesis of novel substituted N-aryl benzamides as hA3G stabilizers and their inhibitory activities against hepatitis C virus replication显示文摘A series of novel amino-substituted N-aryl benzamide analogs were synthesized and evaluated for their ability to inhibit hepatitis C virus(HCV)replication in acutely infected Huh7.5 cells.Most of the substituted N-aryl benzamide compounds showed convincing anti-HCV activities.Compounds 1f,1g and 4c exhibited potent anti-replicative activity at low micromolar levels(IC_(50)=1.0–2.0μM)with selective indices(SI)greater than 40.Mechanistic analysis indicated that the active compounds increased intracellular hA3G protein levels and inhibited HCV replication in a dose-dependent manner.The results demonstrate that this series of substituted Naryl benzamide compounds warrant further investigation as inhibitors of HCV replication. | Yanping Li Zonggen Peng Lanhu Hao Zhouyi Wu Yanping Zhu Laixing Hu Jiandong Jiang Zhuorong Li | 2013 | Acta Pharmaceutica Sinica B2013,3,5: | 2 |
| 5 | Small molecular compounds that inhibit hepatitis C virus replication through destabilizing heat shock cognate 70 messenger RNA显示文摘 | Peng Zonggen Fan Bo Du Nana | 2010 | Hepatology2010,52,3: | 1 |
| 6 | Replication priority of hepatitis C virus genotype 2a in a Chinese cohort显示文摘HCV genotypes have been documented in clinical practice.The aim of this study was to determine the replication priority of different HCV genotypes in a Chinese HCV positive cohort.Serum samples from 491 apparently healthy Chinese blood donors testing positive for HCV antibodies and naive to antiviral drug therapy were tested.Genotyping analysis showed that genotypes 1b and 2a were predominant and accounted for 77.6%of the HCV infections.Among the genotype groups,individuals infected with genotype 2a had an HCV RNA viral load(108 copies/mL)about 200-fold(lg,2.3)greater than those infected with other genotypes(10^(4)–10^(5)copies/mL)indicating a replication priority of genotype 2a.However,there was no correlation between HCV genotype and antibody response suggesting that the amplification advantage of genotype 2a results from a favorable interaction with the host cellular environment.In conclusion,HCV genotypes 1b and 2a are the predominant genotypes in China and genotype 2a possesses a significant replication priority compared with the other genotypes.This suggests the existence of host cellular factors that may act as drug-targets for entirely clearing HCV infection in the future. | Zhen Yang Yongxin Yu Hongzhong Zhang Guifang Shang Jialiang Gao Jian-Dong Jiang Zonggen Peng | 2014 | Acta Pharmaceutica Sinica B2014,4,4: | 0 |
| 7 | Synthesis and antiviral activity of a series of novel N-phenylbenzamide and N-phenylacetophenone compounds as anti-HCV and anti-EV71 agents显示文摘A series of novel N-phenylbenzamide and N-phenylacetophenone compounds were synthesized and evaluated for their antiviral activity against HCV and EV71(strain SZ-98).The biological results showed that three compounds(23,25 and 41) exhibited considerable anti-HCV activity(IC50? 0.57–7.12 μmol/L) and several compounds(23,28,29,30,31 and 42) displayed potent activity against EV71 with the IC50 values lower than 5.00 μmol/L.The potency of compound 23(IC50? 0.57 μmol/L) was superior to that of reported compounds IMB-1f(IC50? 1.90 μmol/L) and IMB-1g(IC50? 1.00 μmol/L) as anti-HCV agents,and compound29 possessed the highest anti-EV71 activity,comparable to the comparator drug pirodavir.The efficacy in vivo and antiviral mechanism of these compounds warrant further investigations. | Zhi Jiang Huiqiang Wang Yanping Li Zonggen Peng Yuhuan Li Zhuorong Li | 2015 | Acta Pharmaceutica Sinica B2015,5,3: | 0 |