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Articles 1 - 7 of 7
Full-Text Articles in Life Sciences
Human Uterine Natural Killer Cells But Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection By Secretion Of Cxcl12, Teddy F. Mselle, Aexandra L. Howell, Mimi Ghosh, Charles R. Wira, Charles L. Sentman
Human Uterine Natural Killer Cells But Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection By Secretion Of Cxcl12, Teddy F. Mselle, Aexandra L. Howell, Mimi Ghosh, Charles R. Wira, Charles L. Sentman
Dartmouth Scholarship
Natural killer (NK) cells derived from the human female reproductive tract (FRT) are phenotypically and functionally distinct from those obtained from peripheral blood. Because the FRT is a primary site of human immunodeficiency virus type 1 (HIV-1) infection in women, we determined whether soluble factors secreted by uterine-derived NK (uNK) cells inhibit HIV-1 infection. Clonal populations of uNK cells were activated with interleukin-12 (IL-12) and IL-15, and conditioned media (CM) from these cultures evaluated for their ability to inhibit infection of cells by HIV-1IIIB, HIV-1NL4.3, and HIV-1HC4 (X4-tropic) or HIV-1BaL (R5-tropic) viruses. We found …
Discovery Of A Non-Peptidic Inhibitor Of West Nile Virus Ns3 Protease By High-Throughput Docking, Dariusz Ekonomiuk, Xun-Cheng Su, Kiyoshi Ozawa, Chrisophe Bodenreider, Siew Pheng Lim, Zheng Yin, Thomas H. Keller, David Beer, Viral Patel, Gottfried Otting, Amedeo Calflisch, Danzhi Huang
Discovery Of A Non-Peptidic Inhibitor Of West Nile Virus Ns3 Protease By High-Throughput Docking, Dariusz Ekonomiuk, Xun-Cheng Su, Kiyoshi Ozawa, Chrisophe Bodenreider, Siew Pheng Lim, Zheng Yin, Thomas H. Keller, David Beer, Viral Patel, Gottfried Otting, Amedeo Calflisch, Danzhi Huang
Faculty of Science - Papers (Archive)
No abstract provided.
Nmr Study Of Complexes Between Low Molecular Mass Inhibitors And The West Nile Virus Ns2b-Ns3 Protease, X Su, Kiyoshi Ozawa, Hiromasa Yagi, S P. Lim, D Wen, D Ekonomiuk, D Huang, T Keller, S Sonntag, A Caflisch, S G. Vasudevan, G Otting
Nmr Study Of Complexes Between Low Molecular Mass Inhibitors And The West Nile Virus Ns2b-Ns3 Protease, X Su, Kiyoshi Ozawa, Hiromasa Yagi, S P. Lim, D Wen, D Ekonomiuk, D Huang, T Keller, S Sonntag, A Caflisch, S G. Vasudevan, G Otting
Faculty of Science - Papers (Archive)
The two-component NS2B-NS3 protease of West Nile virus is essential for its replication and presents an attractive target for drug development. Here, we describe protocols for the high-yield expression of stable isotope-labelled samples in vivo and in vitro. We also describe the use of NMR spectroscopy to determine the binding mode of new low molecular mass inhibitors of the West Nile virus NS2B-NS3 protease which were discovered using high-throughput in vitro screening. Binding to the substrate-binding sites S1 and S3 is confirmed by intermolecular NOEs and comparison with the binding mode of a previously identified low molecular mass inhibitor. Our …
A Fluorescence Quenching Assay To Discriminate Between Specific And Non-Specific Inhibitors Of Dengue Virus Protease, C Bodenreider, D Beer, T Keller, S Sonntag, D Wen, Li Yap, Y H Yau, S G Shocat, D Huang, T Zhou, A Caflisch, X C Su, Kiyoshi Ozawa, G Otting, S G. Vasudevan, J Lescar, S P. Lim
A Fluorescence Quenching Assay To Discriminate Between Specific And Non-Specific Inhibitors Of Dengue Virus Protease, C Bodenreider, D Beer, T Keller, S Sonntag, D Wen, Li Yap, Y H Yau, S G Shocat, D Huang, T Zhou, A Caflisch, X C Su, Kiyoshi Ozawa, G Otting, S G. Vasudevan, J Lescar, S P. Lim
Faculty of Science - Papers (Archive)
In drug discovery, the occurrence of false positives is a major hurdle in the search for lead compounds that can be developed into drugs. A small-molecular-weight compound that inhibits dengue virus protease at low micromolar levels was identified in a screening campaign. Binding to the enzyme was confirmed by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR). However, a structure-activity relationship study that ensued did not yield more potent leads. To further characterize the parental compound and its analogues, we developed a high-speed, low-cost, quantitative fluorescence quenching assay. We observed that specific analogues quenched dengue protease fluorescence and showed …
Nmr Analysis Of The Dynamic Exchange Of The Ns2b Cofactor Between Open And Closed Conformations Of The West Nile Virus Ns2b-Ns3 Protease, X Su, Kiyoshi Ozawa, R Qi, S G. Vasudevan, S P. Lim, G Otting
Nmr Analysis Of The Dynamic Exchange Of The Ns2b Cofactor Between Open And Closed Conformations Of The West Nile Virus Ns2b-Ns3 Protease, X Su, Kiyoshi Ozawa, R Qi, S G. Vasudevan, S P. Lim, G Otting
Faculty of Science - Papers (Archive)
Background: The two-component NS2B-NS3 proteases of West Nile and dengue viruses are essential for viral replication and established targets for drug development. In all crystal structures of the proteases to date, the NS2B cofactor is located far from the substrate binding site (open conformation) in the absence of inhibitor and lining the substrate binding site (closed conformation) in the presence of an inhibitor. Methods: In this work, nuclear magnetic resonance (NMR) spectroscopy of isotope and spin-labeled samples of the West Nile virus protease was used to investigate the occurrence of equilibria between open and closed conformations in solution. Findings: In …
Characterization Of Infectivity And Pathogenesis Of Partially Reconstructed 1918 And Highly Pathogenic Avian Influenza Viruses In The Balb/C Mouse Model, John Allen Pyles
Characterization Of Infectivity And Pathogenesis Of Partially Reconstructed 1918 And Highly Pathogenic Avian Influenza Viruses In The Balb/C Mouse Model, John Allen Pyles
Browse all Theses and Dissertations
Influenza viruses are consistently responsible for an average of 20,000 deaths and 114,000 hospitalizations per year. To a great extent, these viruses always stay one step ahead of the available vaccines and people's immunity year after year because they have the ability to either mutate part of their genetic material, or to be transmitted from one species to another. That same genetic variability explains why highly pathogenic influenza viruses emerge that cause great mortality over several countries resulting in pandemics. Highly pathogenic strains of influenza A virus have emerged occasionally in recent history, producing pandemics such as the one in …
Rhinoviruses: The Quest For A Cure, Michelle Gordon-Grunin
Rhinoviruses: The Quest For A Cure, Michelle Gordon-Grunin
The Science Journal of the Lander College of Arts and Sciences
Rhinoviruses, also known as Human Rhinovirus, abbreviated HRV, are one of the many causes of the common cold. In fact, around 50 percent of all cold are caused by rhinoviruses, with the other major candidates being coronaviruses, influenza A or B virus, and minor causative agents like parainfluenza virus, respiratory syncytial virus, adenovirus, and enterovirus (Makela and Puhakka, 1997). However, due to the complex molecular structure of rhinoviruses, a cure for the common cold caused by HRV is still in the making. Several new treatments have been discovered, impacting the virus as different stages of its life, hopefully to prevent …