Frontiers in Microbiology
·
2019
·
IF 4.259
Xiao Yu,Liu Chunlan,Tang Wei,Zhang Haiwei,Chen Xulin
Chronic hepatitis B (CHB) is a global health problem caused by human hepatitis B virus (HBV). Current treatment with interferons and nucleos(t)ide analogs (NAs) can cause population tolerance and drug resistance. Therefore, new antiviral drugs, especially those targeting host factors, are urgently needed. Here, we identified Evans blue as a new HBV inhibitor by screening an FDA drug library using Huh7DhNTCP cells and confirmed the antiviral activity in primary human hepatocytes and human sodium taurocholate cotransporting polypeptide (hNTCP)-transfected porcine primary hepatocytes. Our efficacy study showed that Evans blue has an IC50 of 2 μM against HBV infection in Huh7DhNTCP cells, and no apparent toxicity at up to 1000 μM. The IC50 of Evans blue against HBV in primary human hepatocytes was approximately 5 μM. Mechanism studies revealed that Evans blue has a dual anti-HBV effect. It inhibits both the binding of viral preS1 to host cells through the host factor NTCP and the virus capsid assembly by targeting the host factor BK channel. The KD of the direct interaction between Evans blue and NTCP is 8.82E-8 M. Evans blue can suppress capsid assembly at micromolar concentrations by reducing the cytosolic calcium ion concentration. Since the antiviral effects on HBV binding and assembly are both achieved through targeting host factors, Evans blue inhibits the infection of nucleos(t)ide analog drug-resistant HBV strains in Huh7DhNTCP cells. Taken together, our results suggest that Evans blue may be a promising anti-HBV drug candidate in the classes of both entry and assembly inhibitors.
研究领域:
病毒学
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肝病学
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药物研发
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DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Xinxin Liu,Tao Liu,Xueli Yuan,Jing Zhang,Mengjiao Zhu,Wei Zhang,Zhenyu Chu,Wanqin Jin
Viral hepatitis is a highly infectious disease caused by various hepatitis viruses that, thus far, have no cure. In early viral invasion, a low viral load in the blood makes early detection difficult unless the symptoms are severe. Herein, a new ultrasensitive and ultrafast hepatitis virus detection strategy is proposed by constructing a dual-surface-activated nanotube that enables recognition probes to not only bind to the outer surface of the nanotube but also penetrate and lock onto its inner surface. This approach significantly enhances both the specific surface area and number of active sites, thereby improving the capture efficiency for traces of hepatitis viral DNA, such as the B type (HBV-DNA). Compared with current DNA detection methods, this approach eliminates the additional amplification steps to achieve an ultralow detection limit of 10 −18 m , advancing the available detection time as early as possible. Using human serum as a sample, this technique enables the precise and quantitative reporting of HBV-DNA within only 15 min and overcomes the interference of usual proteins and other viral DNA. This technique provides new inspiration for quick and early hepatitis diagnosis for in-hospital and non-hospital patients without bulky instruments and complex operations.
研究领域:
生物技术
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医学诊断
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分子生物学
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DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMISTRY
·
2016
·Vol. 34
·期 12
·1353-1359
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IF 1.872
Guangping Liang,Zhanxing Hu,Jie Yuan,Guangyi Liang,Bixue Xu
Matijin-Su ( 1 ) is a phenylalanine dipeptide compound with anti-hepatitis B virus (HBV) activity. Previous reports suggest that the synthesis of glycosylated Matijin-Su derivatives needs at least 10 steps. To simplify the synthetic procedure, we have developed a shorter and more efficient method for the preparation via ultrasound irradiation. Two galactopyranosylated ( 2 ) and two glucopyranosylated ( 3 ) derivatives were synthesized in 6 or 7 steps. The overall yields for the total synthesis of galactopyranosylated derivatives were markedly increased to 39% ( 2a ) or 22% ( 2b ). And the yields for glucopyranosylated derivatives also reached 29% ( 3a ) or 16% ( 3b ).
研究领域:
有机化学
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药物化学
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病毒学
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DOI
高影响因子
MICROCHIMICA ACTA
·
2017
·Vol. 184
·期 11
·4417-4424
·
IF 4.58
Qu Fei,Liu Yining,Kong Rongmei,You Jinmao
The authors report that the fluorescence of polymer-capped silver nanoclusters (AgNCs) is quenched by MoS 2 nanosheets. However, in the presence of electrolytes such as sodium acetate (50 mM), the nanosheets tend to aggregate, and this causes fluorescence to be restored. If, however, ssDNA is added, it will be adsorbed on the surface of the MoS 2 nanosheets and stabilize them against aggregation. As a result, the emission of the AgNCs (best measured at excitation/emission wavelengths of 375/455 nm) is quenched again. If complementary oligonucleotide is added, a dsDNA will be formed that does no longer prevent aggregation and fluorescence is restored. Similarly, if an aptamer is adsorbed on the MoS 2 nanosheets and its substrate is then added to form a folded state, the fluorescence of the AgNCs also will be restored. As a proof of concept, the DNA sequences of hepatitis B virus and of a dopamine-selective aptamer were chosen as models. The resulting assays have low detection limits and linear ranges that extend from 5 to 30 nM for hepatitis B DNA, and from 0.3 to 1 μM for dopamine. In our perception, this method represents a universal platform for the detection of analytes for which complementary oligomers or aptamers are available.
The blue fluorescence of AgNCs is quenched by MoS 2 nanosheets. MoS 2 nanosheets possess different affinity toward single-stranded DNA (ssDNA) versus double-stranded (dsDNA) and folded DNA. Based on this, multiple targets can be detected through changing the sequence of ssDNA.
研究领域:
生物化学
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分子生物学
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纳米技术
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医学检测
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DOI
高影响因子
EMBO REPORTS
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2025
·
IF 6.2
Shuzhi Cui,Wei Gao,Yuxin Chen,Yi Xu,Zhifang Li,Yu Wei,Yaming Jiu
CDC42 is a member of Rho GTPase family that regulates various biological processes and its activity can be hijacked by invading pathogens. Here, we discovered that the level of active CDC42 in hepatocytes positively correlates with the entry capacity of hepatitis B virus (HBV). Mechanistically, CDC42 activation effectively promotes the transport of the viral receptor sodium taurocholate co-transporting polypeptide (NTCP) to the plasma membrane via Rab11 dependent recycling endosomal pathway. NTCP interacts with Rab11 and activation of CDC42 signaling reinforces the interaction between NTCP and Rab11. We further show that clathrin mediated endocytosis (CME), the known HBV entry pathway, is independent of CDC42 activity. Intriguingly, we reveal that CDC42 dependent macropinocytosis is a route for HBV entry, which is equally essential for viral infection as CME. Together, our findings uncover new mechanisms for HBV entry that involve unrecognized functions of CDC42 and suggest that Rho GTPase signaling might represent a potential target for antiviral therapy.
研究领域:
病毒学
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分子生物学
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细胞生物学
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感染性疾病
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肝脏病学
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信号转导
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药理学
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转化医学
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DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2018
·Vol. 411
·期 19
·4569-4576
·
IF 3.307
Wang Kun,Zhai Fu-Heng,He Meng-Qi,Wang Jin,Yu Yong-Liang,He Rong-Huan
A simple fluorescence biosensor is developed based on the enzyme-assisted cascade amplification strategy. The amplification system consists of a hairpin-structure DNA (H-DNA) and exonuclease III. The target DNA can hybridize with the H-DNA and initiate exonuclease III-assisted target recycling amplification to generate abundant G-rich DNA (G-DNA). One region of G-DNA is designed to possess the same sequence as target DNA. Thus, the G-DNA can also hybridize with H-DNA and initiate the digestion of H-DNA. The cascade strategy in this amplification system causes the concentration of G-DNA to grow exponentially. The fluorescence intensity of N -methylmesoporphyrin IX (NMM) is highly enhanced due to the formation of G-quadruplex configuration. Under optimal conditions, the cascade system could achieve an admirable sensitivity with a detection limit of 52 fM for HIV DNA, and guarantees a satisfactory specificity. Moreover, the cascade system could be implemented for other target DNA detections by substituting the recognition region of the H-DNA. In this way, a detection limit of 65 fM for HBV DNA could be achieved by the cascade system. The target DNA analysis in a real serum sample further indicates that this biosensor has potential for future application in clinical diagnosis.
A simple and label-free cascade amplification strategy is developed by exploiting hairpin DNA and EXO III for sensitive DNA detection.
研究领域:
生物化学
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分子生物学
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分析化学
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临床诊断
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DOI
PubMed
高影响因子
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