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131.
Julia Serkedjieva Svetla Danova Iskra Ivanova 《Applied biochemistry and biotechnology》2000,88(1-3):285-298
A novel antibacterial substance produced by Lactobacillus delbrueckii has been isolated and characterized (1). The inhibitory agent corresponded to the criteria for bacteriocins. It was active against lactic acid bacteria (LAB) species
and several food-borne pathogens. The cell-free supernatant was purified by HPLC gel-filtration. Three preparations at different
purification steps were tested for activity on the reproduction of influenza virus A/chicken/Germany, strain Weybridge (H7N7)
and strain Rostock (H7N1) in cell cultures of chicken embryo fibroblasts (CEF). The inhibitory effect was shown to be highly
selective and specific. Expression of viral glycoproteins hemagglutinin, neuraminidase, and nucleoprotein on the surface of
infected cells, virus-induced cytopathic effect, infectious virus yield, and hemagglutinin production were all reduced at
nontoxic concentrations of the crude preparation (B1). B1 did not protect cells from infection, did not affect adsorption,
and slightly inhibited viral penetration into infected cells. The purification did not enhance the cellular toxicity and increased
about 870-fold the virus-inhibitory activity. No inactivating effect on extracellular virus was found. 相似文献
132.
Birch L Murray CW Hartshorn MJ Tickle IJ Verdonk ML 《Journal of computer-aided molecular design》2002,16(12):855-869
Many proteins undergo small side chain or even backbone movements on binding of different ligands into the same protein structure. This is known as induced fit and is potentially problematic for virtual screening of databases against protein targets. In this report we investigate the limits of the rigid protein approximation used by the docking program, GOLD, through cross-docking using protein structures of influenza neuraminidase. Neuraminidase is known to exhibit small but significant induced fit effects on ligand binding. Some neuraminidase crystal structures caused concern due to the bound ligand conformation and GOLD performed poorly on these complexes. A `clean' set, which contained unique, unambiguous complexes, was defined. For this set, the lowest energy structure was correctly docked (i.e. RMSD < 1.5 Å away from the crystal reference structure) in 84% of proteins, and the most promiscuous protein (1mwe) was able to dock all 15 ligands accurately including those that normally required an induced fit movement. This is considerably better than the 70% success rate seen with GOLD against general validation sets. Inclusion of specific water molecules involved in water-mediated hydrogen bonds did not significantly improve the docking performance for ligands that formed water-mediated contacts but it did prevent docking of ligands that displaced these waters. Our data supports the use of a single protein structure for virtual screening with GOLD in some applications involving induced fit effects, although care must be taken to identify the protein structure that performs best against a wide variety of ligands. The performance of GOLD was significantly better than the GOLD implementation of ChemScore and the reasons for this are discussed. Overall, GOLD has shown itself to be an extremely good, robust docking program for this system. 相似文献
133.
Olga V. Andreeva Bulat F. Garifullin Vladimir V. Zarubaev Alexander V. Slita Iana L. Yesaulkova Alexandrina S. Volobueva Mayya G. Belenok Maria A. Mankova Liliya F. Saifina Marina M. Shulaeva Alexandra D. Voloshina Anna P. Lyubina Vyacheslav E. Semenov Vladimir E. Kataev 《Molecules (Basel, Switzerland)》2021,26(12)
A series of 1,2,3-triazolyl nucleoside analogues in which 1,2,3-triazol-4-yl-β-d-ribofuranosyl fragments are attached via polymethylene linkers to both nitrogen atoms of the heterocycle moiety (uracil, 6-methyluracil, thymine, quinazoline-2,4-dione, alloxazine) or to the C-5 and N-3 atoms of the 6-methyluracil moiety was synthesized. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. Antiviral assays revealed three compounds, 2i, 5i, 11c, which showed moderate activity against influenza virus A H1N1 with IC50 values of 57.5 µM, 24.3 µM, and 29.2 µM, respectively. In the first two nucleoside analogues, 1,2,3-triazol-4-yl-β-d-ribofuranosyl fragments are attached via butylene linkers to N-1 and N-3 atoms of the heterocycle moiety (6-methyluracil and alloxazine, respectively). In nucleoside analogue 11c, two 1,2,3-triazol-4-yl-2′,3′,5′-tri-O-acetyl-β-d-ribofuranose fragments are attached via propylene linkers to the C-5 and N-3 atoms of the 6-methyluracil moiety. Almost all synthesized 1,2,3-triazolyl nucleoside analogues showed no antiviral activity against the coxsackie B3 virus. Two exceptions are 1,2,3-triazolyl nucleoside analogs 2f and 5f, in which 1,2,3-triazol-4-yl-2′,3′,5′-tri-O-acetyl-β-d-ribofuranose fragments are attached to the C-5 and N-3 atoms of the heterocycle moiety (6-methyluracil and alloxazine respectively). These compounds exhibited high antiviral potency against the coxsackie B3 virus with IC50 values of 12.4 and 11.3 µM, respectively, although both were inactive against influenza virus A H1N1. According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 2i, 5i, and 11c against the H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRp). As to the antiviral activity of nucleoside analogs 2f and 5f against coxsackievirus B3, it can be explained by their interaction with the coat proteins VP1 and VP2. 相似文献
134.
对一株于2005年从浙江省分离获得的禽流感病毒株(A/Chicken/zhejiang/24/2005)进行了鉴定、全基因组序列测定、分析和致病性研究.经血凝抑制试验和神经氨酸酶抑制试验证实,此分离病毒株为H5NI亚型.对该毒株的全基因组序列测定和分析显示,HA蛋白在HA1和HA2连接处,含有连续多碱性氨基酸模体(-RRKKR-).进化分析结果表明,A/Chicken/zhejiang/24/2005(H5N1)7个基因来源于2004~2005年湖南地区流行株,但PB1基因来源于未知野禽毒株.动物实验结果显示,Ck/ZJ/24/05对鸡和鸭均具有高致病性,对小鼠无致病性,与HA的序列特征相符合. 相似文献
135.
运用柔性分子对接和分子动力学方法, 深入研究了4-(氮乙酰氨基)-5-胍基-3-(3-戊氧基)安息香酸(BA)与各类型神经氨酸酶(N1, N2, N9亚型和B型)间的作用机制. 结果显示, BA与各类型神经氨酸酶结合模式存在差异, 但作用机制比较相似: 与它们的活性腔均匹配良好, 并形成稳定的复合体系, 最大结合能分别等于-1233.62, -1385.72, -663.11, -1058.87 kJ•mol-1. 这表明BA对各类型神经氨酸酶均有良好的抑制效果. 进一步分析发现, BA与各类型神经氨酸酶活性腔内保守关键氨基酸残基发生较强的静电和氢键作用, 而与易突变氨基酸残基作用较弱, 表明了活性腔内易突变氨基酸残基发生突变也不会对抑制效果造成明显影响. 因此, BA是一种极具应用前景的新型抗流感病毒药物. 结合以前的研究结果, 我们提出了以BA为底物的抗流感病毒药物的修饰方向. 相似文献
136.
137.
138.
Influenza outbreaks pose a serious threat to human health. Hemagglutinin (HA) is an important target for influenza virus entry inhibitors. In this study, we synthesized four pentacyclic triterpene conjugates with a sialylglycopeptide scaffold through the Cu(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC) and prepared affinity assays of these conjugates with two HAs, namely H1N1 (A/WSN/1933) and H5N1 (A/Hong Kong/483/97), respectively. With a dissociation constant (KD) of 6.89 μM, SCT-Asn-betulinic acid exhibited the strongest affinity with the H1N1 protein. Furthermore, with a KD value of 9.10 μM, SCT-Asn-oleanolic acid exhibited the strongest affinity with the H5N1 protein. The conjugates considerably enhanced antiviral activity, which indicates that pentacyclic triterpenes can be used as a ligand to improve the anti-influenza ability of the sialylglycopeptide molecule by acting on the HA protein. 相似文献
139.
140.
In this paper,a reaction-diffusion system is proposed to investigate avian-human influenza.Two free boundaries are introduced to describe the spreading frontiers of the avian influenza.The basic reproduction numbers rF0(t)and RF0(t)are defined for the bird with the avian influenza and for the human with the mutant avian influenza of the free boundary problem,respectively.Properties of these two time-dependent basic reproduction numbers are obtained.Sufficient conditions both for spreading and for vanishing of the avian influenza are given.It is shown that if rF0(0)<1 and the initial number of the infected birds is small,the avian influenza vanishes in the bird world.Furthermore,if rF0(0)<1 and RF0(0)<1,the avian influenza vanishes in the bird and human worlds.In the case that rF0(0)<1 and RF0(0)>1,spreading of the mutant avian influenza in the human world is possible.It is also shown that if rF0(t0)>1 for any t0>0,the avian influenza spreads in the bird world. 相似文献