• 1 Ion channels as antivirus targets. 复制标题 收藏 收藏

    【离子通道作为防病毒目标。】 复制标题 收藏 收藏
    DOI:10.1007/s12250-010-3136-y 复制DOI
    作者列表:Liang X,Li ZY
    BACKGROUND & AIMS: :Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a change of electrochemical or proton gradient across the bilayer lipid membrane which modulates viral or cellular activity. We will discuss a group of viral channel proteins that belong to the viroproin family, and which participate in a number of viral functions including promoting the release of viral particles from cells. Blocking these channel-forming proteins may be "lethal", which can be a suitable and potential therapeutic strategy. In this review we discuss seven ion channels of viruses which can lead serious infections in human beings: M2 of influenza A, NB and BM2 of influenza B, CM2 of influenza C, Vpu of HIV-1, p7 of HCV and 2B of picornaviruses.
    背景与目标: 离子通道是在许多病毒中发现的膜蛋白,在病毒生命周期中具有至关重要的生理意义。它们有一个共同的特征,即它们的作用模式涉及跨双层脂质膜的电化学或质子梯度的变化,从而调节病毒或细胞活性。我们将讨论一组属于病毒体蛋白家族的病毒通道蛋白,它们参与许多病毒功能,包括促进病毒颗粒从细胞中释放。阻断这些通道形成蛋白可能是 “致命的”,这可能是一种合适且潜在的治疗策略。在这篇综述中,我们讨论了可导致人类严重感染的病毒的七个离子通道: 甲型流感的M2,乙型流感的NB和BM2,丙型流感的CM2,HIV-1的Vpu,HCV的p7和小核糖核酸病毒的2B。
  • 【病毒成分合成和抗病毒免疫过程中使用的遗传信息。】 复制标题 收藏 收藏
    DOI:10.1038/206343a0 复制DOI
    作者列表:Mekler LB
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【标准治疗失败后,重组抗肿瘤和抗病毒蛋白注射液与安慰剂相比在转移性结直肠癌中的II期研究。】 复制标题 收藏 收藏
    DOI:10.1634/theoncologist.2014-0439 复制DOI
    作者列表:Jia R,Wang Y,Mao XY,Li SS,Xu N,Xiong JP,Shen L,Bai L,Liu W,Liu LJ,Ge FJ,Chen YL,Lin L,Xu JM
    BACKGROUND & AIMS: LESSONS LEARNED:Novaferon showed moderate efficacy and was well-tolerated in patients with metastatic colorectal cancer (mCRC), especially with the 20 μg injected 3 times a week strategy.Although Novaferon did not provide a survival benefit for mCRC patients who have failed standard treatment, it may play a role in improvement of immune function. BACKGROUND:To observe the efficacy, safety, and optimal dosage of recombinant antitumor and antivirus protein (Novaferon) in treating patients with metastatic colorectal cancer (mCRC) who failed at least two prior palliative regimens. METHODS:We enrolled 108 patients from May 2011 to December 2012. According to different treatment modalities and therapeutic dosages, the participants were randomly divided into four cohorts at a 2:2:2:1 ratio: (a) 20 μg Novaferon (Genova Biotech, Beijing, People's Republic of China, http://www.genovabiotech.net) injected twice per week, (b) 20 μg Novaferon injected 3 times per week, (c) 40 μg Novaferon injected 3 times per week, or (d) saline injected 3 times per week. The primary endpoint was overall survival. RESULTS:There was no significant difference in overall survival among the four cohorts. The 20-μg dose of Novaferon injected 3 times per week had the highest disease control rate (44.0%) at 6 weeks but without significant differences when compared with placebo (p = .159). Major adverse events with Novaferon were influenza-like symptoms, bone marrow suppression, liver dysfunction, and gastrointestinal discomfort. The level of natural killer cells increased and regulatory T cells decreased significantly after treatment with Novaferon, whereas levels in the placebo group remained the same. CONCLUSION:Novaferon showed moderate efficacy and was well tolerated in patients with mCRC, especially with the 20-μg dose injected 3 times per week. Furthermore, Novaferon might improve immune function of these patients.
    背景与目标:
  • 【牡荆中的Labdane型二萜类化合物及其抗病毒活性。】 复制标题 收藏 收藏
    DOI:10.1007/s11418-017-1125-2 复制DOI
    作者列表:Ban NK,Thoa NTK,Linh TM,Trang DT,Van Kiem P,Nhiem NX,Tai BH,Van Minh C,Song JH,Ko HJ,Kim SH
    BACKGROUND & AIMS: :Phytochemical investigation of the methanol extract of Vitex limonifolia leaves led to the isolation of three new labdane-type diterpenoids, vitexlimolides A-C (1-3) and eight known compounds, 5,4'-dihydroxy-3,7-dimethoxyflavone (4), vitecetin (5), 5,4'-dihydroxy-7,3'-dimethoxyflavone (6), verrucosin (7), 2α, 3α-dihydroxy-urs-12-en-28-oic acid (8), euscaphlic acid (9), 18,19-seco, 2α, 3α-dihydroxy-19-oxo-urs-11,13(18)-dien-28-oic acid (10), and maslinic acid (11). Their chemical structures were elucidated by physical and chemical methods. All compounds were evaluated for antiviral activities against CVB3, HRV1B, and EV71 viruses. As a result, compounds 4 and 6 showed potent antiviral activity against CVB3 infection with IC50 values of 0.12 ± 0.06 and 1.86 ± 0.18 (µM), respectively.
    背景与目标: : 对牡荆叶片甲醇提取物的植物化学研究导致隔离出三种新的labdane型二萜类化合物,牡荆内酯A-C (1-3) 和八种已知化合物,5,4 '-dihydroxy-3,7-二甲氧基黄酮 (4),vitecetin (5),5,4'-dihydroxy-7,3 '-二甲氧基黄酮 (6),verrucosin (7),2α,3α-二羟基-urs-12-en-28-oic酸 (8),白沙糖酸 (9),18,19-seco,2α,3α-二羟基-19-oxo-urs-11,13(18)-dien-28-oic (10) 和山糖油酸 (11)。通过物理和化学方法阐明了它们的化学结构。评估了所有化合物对CVB3,HRV1B和EV71病毒的抗病毒活性。结果,化合物4和6显示出针对CVB3感染的有效抗病毒活性,IC50值分别为0.12 ± 0.06和1.86 ± 0.18 (µ m)。
  • 【一种新型牛IFN-omega24的表征和抗病毒活性。】 复制标题 收藏 收藏
    DOI:10.1016/j.molimm.2015.04.009 复制DOI
    作者列表:Luo X,Guo Y,Bao J,Liu Y,An D,Ma B,Gao M,Wang J
    BACKGROUND & AIMS: :A novel bovine interferon-ω (BoIFN-ω) gene, which encodes a protein of 195 amino acids with a 23-amino acid signal peptide, was amplified from bovine liver genomic DNA through PCR and named BoIFN-ω24 according to its position in the bovine genome. In this study, the recombinant protein was expressed in Escherichia coli and antiviral or antiproliferation activity was determined in vitro. Results showed that BoIFN-ω24 exhibits high antiviral activity, which can be abrogated using PAb against BoIFN-ω24, and inhibits cell proliferation. BoIFN-ω24 also presents high sensitivity to trypsin and stability at pH 2.0 or 65°C, which are typical characteristics of type I IFN. This study revealed that BoIFN-ω24 is a potential novel effective therapeutic agent and provided a basis for further research on the BoIFN-ω multigene family.
    背景与目标: : 通过PCR从牛肝基因组DNA中扩增出一个新的牛干扰素-ω (BoIFN-ω) 基因,该基因编码具有23个氨基酸信号肽的195个氨基酸的蛋白质,并根据其在牛基因组中的位置将其命名为BoIFN-ω24。在这项研究中,重组蛋白在大肠杆菌中表达,并在体外确定了抗病毒或抗增殖活性。结果表明,BoIFN-ω24具有很高的抗病毒活性,可以使用PAb消除BoIFN-ω24,并抑制细胞增殖。BoIFN-ω24还表现出对胰蛋白酶的高灵敏度和在pH 2.0或65 °C下的稳定性,这是I型IFN的典型特征。这项研究表明,BoIFN-ω24是一种潜在的新型有效治疗剂,并为进一步研究BoIFN-ω 多基因家族提供了基础。
  • 【多发性硬化症的抗病毒免疫活性与MRI活性相关。】 复制标题 收藏 收藏
    DOI:10.1111/ane.12417 复制DOI
    作者列表:Latham LB,Lee MJ,Lincoln JA,Ji N,Forsthuber TG,Lindsey JW
    BACKGROUND & AIMS: OBJECTIVE:The objective of this study was to determine whether reactivation of Epstein-Barr (EBV) or activation of the anti-EBV immune response correlates with MS disease activity on MR imaging. METHODS:Subjects with early, active relapsing-remitting MS were studied for 16 weeks with blood and saliva samples collected every 2 weeks and brain MRI performed every 4 weeks. We isolated peripheral blood mononuclear cells from each blood sample and tested the immune response to EBV, autologous EBV-infected lymphoblastoid cell lines (LCL), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), tetanus, and mitogens. We measured the proliferative response and the number of interferon-γ secreting cells with ELISPOT. We measured the amounts of EBV, HHV6, and VZV DNA in blood and saliva with quantitative PCR. On MRI, we measured number and volume of contrast enhancing and T2 lesions. We tested for correlation between the immunologic assays and the MRI results, assessing different time intervals between the MRI and immunologic assays. RESULTS:We studied 20 subjects. Ten had enhancing lesions on one or more MRI scans and one had new T2 lesions without enhancement. The most significant correlation was between proliferation to autologous LCL and the number of combined unique active lesions on MRI 4 weeks later. Both proliferation and number of cells secreting interferon-γ in response to LCL correlated with the number of enhancing lesions 8 weeks later. CONCLUSIONS:We find evidence for correlation of antiviral immune responses in the blood with subsequent disease activity on MRI scans.
    背景与目标:
  • 【定义NF-κ b在抗病毒反应中的新兴作用: 重新审视干扰素-β 增强体范式。】 复制标题 收藏 收藏
    DOI:10.1371/journal.ppat.1002165 复制DOI
    作者列表:Balachandran S,Beg AA
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【蓝桉果实中抗病毒成分的肠通透性。在Caco-2细胞模型中。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmcl.2006.11.021 复制DOI
    作者列表:Yang XW,Guo QM,Wang Y,Xu W,Tian L,Tian XJ
    BACKGROUND & AIMS: :The uptake and transepithelial transport of the three main constituents macrocarpal A (M-A), macrocarpal B (M-B), and cypellocarpa C (Cy-C) from the fruits of Eucalyptus globulus Labill. were investigated. Monolayers of the human intestinal epithelial cancer cell line Caco-2 were incubated with M-A, M-B, and Cy-C to model its intestinal absorption and transport, respectively. The determination of compounds was performed by HPLC. The apparent permeability coefficients (P(app)) for M-A, M-B, and Cy-C in the apical-to-basolateral direction of a Caco-2 monolayer were (1.70+/-0.06)x10(-6), (1.99+/-0.10)x10(-6), and (6.08+/-0.41)x10(-6)cm/s, respectively. In the presence of iodoacetamide, the P(app) of Cy-C were both reducted in apical-to-basolateral and basolateral-to-apical directions. M-A and M-B appear to accumulate in the epithelial cells. The intestinal absorption of M-A, M-B, and Cy-C was passive diffusion as the dominating process and Cy-C was partly ATP-dependent.
    背景与目标: : 桉树果实中三种主要成分大腕A (m-a),大腕B (m-b) 和cypellocarpa C (cy-c) 的吸收和跨上皮运输。被调查。将人肠上皮癌细胞系Caco-2的单层分别与m-a,m-b和cy-c孵育,以模拟其肠吸收和转运。化合物的测定通过HPLC进行。M-A、M-B和Cy-C在Caco-2单层的顶端至基底外侧方向的表观渗透系数 (P(app)) 为 (1.70 +/-0.06)x10(-6),(1.99 +/-0.10)x10(-6) 和 (6.08 +/-0.41)x10(-6)cm/s。在存在碘乙酰胺的情况下,Cy-C的P(app) 均在顶端至基底外侧和基底外侧至顶端方向上还原。M-a和m-b似乎积聚在上皮细胞中。M-A,M-B和Cy-C的肠道吸收是被动扩散的主要过程,而Cy-C部分依赖于ATP。
  • 【cis-vaccenic酸 (一种来自荚膜红假单胞菌的抗病毒物质) 以及不饱和脂肪酸和相关醇对T5噬菌体的灭活。】 复制标题 收藏 收藏
    DOI:10.1016/0378-1097(91)90006-v 复制DOI
    作者列表:Hirotani H,Ohigashi H,Kobayashi M,Koshimizu K,Takahashi E
    BACKGROUND & AIMS: :The antiviral extract from Rhodopseudomonas capsulata was purified and the predominant active component was defined as cis-vaccenic acid (Cl-8:1 delta 11) by gas-liquid chromatography and gas chromatography-mass spectrometry analyses. Antiviral activities of unsaturated fatty acids and related alcohols against T5 phage were also tested. Among them, linoelaidic acid, oleic acid, and petroselenyl alcohol inactivated 98%, 53%, 67% of T5 phage at the concentration of 50 micrograms/ml, respectively.
    背景与目标: : 通过气相色谱和气相色谱-质谱分析,纯化了荚膜红假单胞菌的抗病毒提取物,并将主要活性成分定义为顺式疫苗酸 (Cl-8:1 delta 11)。还测试了不饱和脂肪酸和相关醇对T5噬菌体的抗病毒活性。其中,亚麻酸,油酸和石油硒醇分别以50微克/毫升的浓度灭活T5噬菌体的98%,53%,67%。
  • 【鸡 β 干扰素的表达、纯化及其抗病毒免疫活性。】 复制标题 收藏 收藏
    DOI:10.1016/j.pep.2012.04.014 复制DOI
    作者列表:Cai M,Zhu F,Shen P
    BACKGROUND & AIMS:
    背景与目标:
  • 【在鼠巨细胞病毒感染过程中,抗病毒抗体依赖性细胞介导的细胞毒性。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Manischewitz JE,Quinnan GV Jr
    BACKGROUND & AIMS:
    背景与目标:
  • 【在抗病毒化疗中具有临床潜力的核苷类似物。几种胸苷和2 '-脱氧胞苷类似物5'-三磷酸对纯化的人 (α,β) 和单纯疱疹病毒 (1、2型) DNA聚合酶的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Ruth JL,Cheng YC
    BACKGROUND & AIMS:
    背景与目标:
  • 【抗病毒剂remantadine和金刚烷胺与脂质膜的相互作用以及对人红细胞曲率的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Tverdislov VA,el-Karadagi S,Kharitonenkov IG,Glaser R,Donath E,Herrmann A,Lentzsch P,Donath J
    BACKGROUND & AIMS: :Surface potential difference, conductance, and elasticity changes of bilayer lipid membranes induced by the antivirus drugs amantadine and remantadine were measured. An influence on the human erythrocyte shape was shown. Both drugs are stomatocytogenic. The adsorption at the cytoplasmatic membrane was electrophoretically proved. The heat-induced vesiculation is partly inhibited. No microvesicles were observed. Instead, large tails which did not detach from the cell body were seen. The general conclusion is that these amphiphilic adamantane derivatives are membrane agents which modify membrane interaction processes, possibly by influencing the bending properties.
    背景与目标: : 测量了抗病毒药物金刚烷胺和remantadine引起的双层脂质膜的表面电位差,电导和弹性变化。显示了对人红细胞形状的影响。两种药物都是造口剂。电泳证明了在细胞质膜上的吸附。热诱导的囊泡被部分抑制。未观察到微泡。相反,看到了没有从细胞体上脱离的大尾巴。一般结论是,这些两亲性金刚烷衍生物是膜剂,可能通过影响弯曲性能来改变膜相互作用过程。
  • 【CRISPR-Cas系统在细菌抗病毒免疫和DNA修复中的双重功能。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2958.2010.07465.x 复制DOI
    作者列表:Babu M,Beloglazova N,Flick R,Graham C,Skarina T,Nocek B,Gagarinova A,Pogoutse O,Brown G,Binkowski A,Phanse S,Joachimiak A,Koonin EV,Savchenko A,Emili A,Greenblatt J,Edwards AM,Yakunin AF
    BACKGROUND & AIMS: :Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and the associated proteins (Cas) comprise a system of adaptive immunity against viruses and plasmids in prokaryotes. Cas1 is a CRISPR-associated protein that is common to all CRISPR-containing prokaryotes but its function remains obscure. Here we show that the purified Cas1 protein of Escherichia coli (YgbT) exhibits nuclease activity against single-stranded and branched DNAs including Holliday junctions, replication forks and 5'-flaps. The crystal structure of YgbT and site-directed mutagenesis have revealed the potential active site. Genome-wide screens show that YgbT physically and genetically interacts with key components of DNA repair systems, including recB, recC and ruvB. Consistent with these findings, the ygbT deletion strain showed increased sensitivity to DNA damage and impaired chromosomal segregation. Similar phenotypes were observed in strains with deletion of CRISPR clusters, suggesting that the function of YgbT in repair involves interaction with the CRISPRs. These results show that YgbT belongs to a novel, structurally distinct family of nucleases acting on branched DNAs and suggest that, in addition to antiviral immunity, at least some components of the CRISPR-Cas system have a function in DNA repair.
    背景与目标: : 聚集的规则间隔的短回文重复序列 (CRISPRs) 和相关蛋白 (Cas) 构成了针对原核生物中病毒和质粒的适应性免疫系统。Cas1是一种与CRISPR相关的蛋白质,对所有含CRISPR的原核生物都很常见,但其功能仍然不清楚。在这里,我们显示了大肠杆菌 (YgbT) 的纯化Cas1蛋白对单链和分支dna (包括Holliday连接,复制叉和5'-皮瓣) 具有核酸酶活性。YgbT的晶体结构和定点诱变揭示了潜在的活性位点。全基因组屏幕显示,YgbT与DNA修复系统的关键组件 (包括recB,recC和ruvB) 在物理和遗传上相互作用。与这些发现一致,ygbT缺失菌株显示出对DNA损伤的敏感性增加,染色体分离受损。在CRISPR簇缺失的菌株中观察到类似的表型,表明YgbT在修复中的功能涉及与CRISPR的相互作用。这些结果表明,YgbT属于作用于分支DNA的新型,结构上不同的核酸酶家族,并表明,除了抗病毒免疫外,CRISPR-Cas系统的至少某些组件在DNA修复中具有功能。
  • 【CARF域超家族的进化和功能分类,原核杀毒防御中的关键传感器。】 复制标题 收藏 收藏
    DOI:10.1093/nar/gkaa635 复制DOI
    作者列表:Makarova KS,Timinskas A,Wolf YI,Gussow AB,Siksnys V,Venclovas Č,Koonin EV
    BACKGROUND & AIMS: :CRISPR-associated Rossmann Fold (CARF) and SMODS-associated and fused to various effector domains (SAVED) are key components of cyclic oligonucleotide-based antiphage signaling systems (CBASS) that sense cyclic oligonucleotides and transmit the signal to an effector inducing cell dormancy or death. Most of the CARFs are components of a CBASS built into type III CRISPR-Cas systems, where the CARF domain binds cyclic oligoA (cOA) synthesized by Cas10 polymerase-cyclase and allosterically activates the effector, typically a promiscuous ribonuclease. Additionally, this signaling pathway includes a ring nuclease, often also a CARF domain (either the sensor itself or a specialized enzyme) that cleaves cOA and mitigates dormancy or death induction. We present a comprehensive census of CARF and SAVED domains in bacteria and archaea, and their sequence- and structure-based classification. There are 10 major families of CARF domains and multiple smaller groups that differ in structural features, association with distinct effectors, and presence or absence of the ring nuclease activity. By comparative genome analysis, we predict specific functions of CARF and SAVED domains and partition the CARF domains into those with both sensor and ring nuclease functions, and sensor-only ones. Several families of ring nucleases functionally associated with sensor-only CARF domains are also predicted.
    背景与目标: : 与CRISPR相关的Rossmann Fold (CARF) 和SMODS相关并融合到各种效应域 (SAVED) 是基于环状寡核苷酸的抗噬菌体信号传导系统 (CBASS) 的关键成分,该系统可感测环状寡核苷酸并将信号传递给诱导细胞休眠或死亡的效应子。大多数CARF是III型CRISPR-Cas系统中内置的cps的组成部分,其中CARF结构域结合由Cas10聚合酶环化酶合成的环状寡核苷酸 (cOA),并通过变构激活效应物,通常是混杂的核糖核酸酶。此外,该信号传导途径包括环核酸酶,通常还包括切割cOA并减轻休眠或死亡诱导的CARF结构域 (传感器本身或专用酶)。我们介绍了细菌和古细菌中CARF和保存域的全面普查,以及它们基于序列和结构的分类。有10个主要的CARF结构域家族和多个较小的基团,它们在结构特征,与不同效应物的关联以及环核酸酶活性的存在与否方面有所不同。通过比较基因组分析,我们预测了CARF和保存的结构域的特定功能,并将CARF结构域划分为具有传感器和环核酸酶功能的结构域,以及仅具有传感器功能的结构域。还预测了与仅传感器CARF结构域功能相关的几个环核酸酶家族。

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