scholarly journals Mucin‐Inspired, High Molecular Weight Virus Binding Inhibitors Show Biphasic Binding Behavior to Influenza A Viruses

Small ◽  
2020 ◽  
Vol 16 (47) ◽  
pp. 2004635
Author(s):  
Matthias Wallert ◽  
Chuanxiong Nie ◽  
Parambath Anilkumar ◽  
Srinivas Abbina ◽  
Sumati Bhatia ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Virus Binding ◽  
Binding Behavior ◽  
Binding Inhibitors

scholarly journals Membrane-tethered mucin-like polypeptides sterically inhibit binding and slow fusion kinetics of influenza A virus

2020 ◽  
Vol 117 (23) ◽  
pp. 12643-12650 ◽  
Author(s):  
Corleone S. Delaveris ◽  
Elizabeth R. Webster ◽  
Steven M. Banik ◽  
Steven G. Boxer ◽  
Carolyn R. Bertozzi
Keyword(s):  
Lipid Bilayers ◽  
Influenza A ◽  
Conformational Transition ◽  
Molecular Model ◽  
High Surface ◽  
Protective Mechanism ◽  
Dependent Manner ◽  
Influenza A Viruses ◽  
Virus Binding ◽  
Kinetics Of

The mechanism(s) by which cell-tethered mucins modulate infection by influenza A viruses (IAVs) remain an open question. Mucins form both a protective barrier that can block virus binding and recruit IAVs to bind cells via the sialic acids of cell-tethered mucins. To elucidate the molecular role of mucins in flu pathogenesis, we constructed a synthetic glycocalyx to investigate membrane-tethered mucins in the context of IAV binding and fusion. We designed and synthesized lipid-tethered glycopolypeptide mimics of mucins and added them to lipid bilayers, allowing chemical control of length, glycosylation, and surface density of a model glycocalyx. We observed that the mucin mimics undergo a conformational change at high surface densities from a compact to an extended architecture. At high surface densities, asialo mucin mimics inhibited IAV binding to underlying glycolipid receptors, and this density correlated to the mucin mimic’s conformational transition. Using a single virus fusion assay, we observed that while fusion of virions bound to vesicles coated with sialylated mucin mimics was possible, the kinetics of fusion was slowed in a mucin density-dependent manner. These data provide a molecular model for a protective mechanism by mucins in IAV infection, and therefore this synthetic glycocalyx provides a useful reductionist model for studying the complex interface of host–pathogen interactions.

scholarly journals Membrane-Tethered Mucin-like Polypeptides Sterically Inhibit Binding and Slow Fusion Kinetics of Influenza A Virus

2019 ◽  
Author(s):  
Corleone Delaveris ◽  
Elizabeth Webster ◽  
Steven Banik ◽  
Steven Boxer ◽  
Carolyn Bertozzi
Keyword(s):  
Lipid Bilayers ◽  
Influenza A ◽  
Conformational Transition ◽  
Molecular Model ◽  
High Surface ◽  
Protective Mechanism ◽  
Dependent Manner ◽  
Influenza A Viruses ◽  
Virus Binding ◽  
Kinetics Of

<div> <div> <div> <p>The mechanism(s) by which cell-tethered mucins modulate infection by Influenza A viruses (IAVs) remains an open question. Mucins form both a protective barrier that can block virus binding and recruit IAVs to bind cells via the sialic acids of cell-tethered mucins. To elucidate the molecular role of mucins in flu pathogenesis, we constructed a synthetic glycocalyx to investigate membrane-tethered mucins in the context of IAV binding and fusion. We designed and synthesized lipid-tethered glycopolypeptide mimics of mucins and added them to lipid bilayers, allowing chemical control of length, glycosylation, and surface density of a model glycocalyx. We observed that the mucin mimics undergo a conformational change at high surface densities from a compact to an extended architecture. At high surface densities asialo mucin mimics inhibited IAV binding to underlying glycolipid receptors and this density correlated to the mucin mimic’s conformational transition. Using a single virus fusion assay, we observed that while fusion of virions bound to vesicles coated with sialylated mucin mimics was possible, the kinetics of fusion were slowed in a mucin density-dependent manner. These data provide a molecular model for a protective mechanism by mucins in IAV infection, and therefore this synthetic glycocalyx provides a useful reductionist model for studying the complex interface of host-pathogen interactions. </p> </div> </div> </div>

scholarly journals Membrane-Tethered Mucin-like Polypeptides Sterically Inhibit Binding and Slow Fusion Kinetics of Influenza A Virus

2019 ◽  
Author(s):  
Corleone Delaveris ◽  
Elizabeth Webster ◽  
Steven Banik ◽  
Steven Boxer ◽  
Carolyn Bertozzi
Keyword(s):  
Lipid Bilayers ◽  
Influenza A ◽  
Conformational Transition ◽  
Molecular Model ◽  
High Surface ◽  
Protective Mechanism ◽  
Dependent Manner ◽  
Influenza A Viruses ◽  
Virus Binding ◽  
Kinetics Of

<div> <div> <div> <p>The mechanism(s) by which cell-tethered mucins modulate infection by Influenza A viruses (IAVs) remains an open question. Mucins form both a protective barrier that can block virus binding and recruit IAVs to bind cells via the sialic acids of cell-tethered mucins. To elucidate the molecular role of mucins in flu pathogenesis, we constructed a synthetic glycocalyx to investigate membrane-tethered mucins in the context of IAV binding and fusion. We designed and synthesized lipid-tethered glycopolypeptide mimics of mucins and added them to lipid bilayers, allowing chemical control of length, glycosylation, and surface density of a model glycocalyx. We observed that the mucin mimics undergo a conformational change at high surface densities from a compact to an extended architecture. At high surface densities asialo mucin mimics inhibited IAV binding to underlying glycolipid receptors and this density correlated to the mucin mimic’s conformational transition. Using a single virus fusion assay, we observed that while fusion of virions bound to vesicles coated with sialylated mucin mimics was possible, the kinetics of fusion were slowed in a mucin density-dependent manner. These data provide a molecular model for a protective mechanism by mucins in IAV infection, and therefore this synthetic glycocalyx provides a useful reductionist model for studying the complex interface of host-pathogen interactions. </p> </div> </div> </div>

Microtubule motors and other maps

1990 ◽  
Vol 48 (3) ◽  
pp. 1-1
Author(s):  
Richard B. Vallee
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Cytoplasmic Dynein ◽  
Organelle Transport ◽  
Structural Components ◽  
Microtubule Associated Proteins ◽  
Microtubule Motors ◽  
Associated Proteins ◽  
The Subject ◽  
Intracellular Motility

Microtubules are involved in a number of forms of intracellular motility, including mitosis and bidirectional organelle transport. Purified microtubules from brain and other sources contain tubulin and a diversity of microtubule associated proteins (MAPs). Some of the high molecular weight MAPs - MAP 1A, 1B, 2A, and 2B - are long, fibrous molecules that serve as structural components of the cytamatrix. Three MAPs have recently been identified that show microtubule activated ATPase activity and produce force in association with microtubules. These proteins - kinesin, cytoplasmic dynein, and dynamin - are referred to as cytoplasmic motors. The latter two will be the subject of this talk.Cytoplasmic dynein was first identified as one of the high molecular weight brain MAPs, MAP 1C. It was determined to be structurally equivalent to ciliary and flagellar dynein, and to produce force toward the minus ends of microtubules, opposite to kinesin.

TMPRSS2 is essential for pathogenicity of H7N9 and H1N1 influenza A viruses in mice

Pneumologie ◽  
2014 ◽  
Vol 68 (02) ◽  
Author(s):  
C Tarnow ◽  
G Engels ◽  
A Arendt ◽  
F Schwalm ◽  
H Sediri ◽  
...  
Keyword(s):  
Influenza A ◽  
H1n1 Influenza ◽  
Influenza A Viruses

Killing two birds with one stone – Prenylated flavonoids disrupt the lethal synergism of influenza A viruses and pneumococci

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
U Grienke ◽  
M Richter ◽  
E Walther ◽  
A Hoffmann ◽  
J Kirchmair ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza A Viruses ◽  
Prenylated Flavonoids

Studies on the Functionality of Newly Synthesized Fibrinogen after Treatment of Acute Myocardial Infarction with Streptokinase, Increase in the Rate of Fibrinopeptide Release

1993 ◽  
Vol 70 (06) ◽  
pp. 0978-0983 ◽  
Author(s):  
Edelmiro Regano ◽  
Virtudes Vila ◽  
Justo Aznar ◽  
Victoria Lacueva ◽  
Vicenta Martinez ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Molecular Weight ◽  
Steady State ◽  
High Molecular Weight ◽  
Coronary Arteries ◽  
Risk Index ◽  
Weight Fraction ◽  
High Molecular Weight Fraction ◽  
Fibrinopeptide A

SummaryIn 15 patients with acute myocardial infarction who received 1,500,000 U of streptokinase, the gradual appearance of newly synthesized fibrinogen and the fibrinopeptide release during the first 35 h after SK treatment were evaluated. At 5 h the fibrinogen circulating in plasma was observed as the high molecular weight fraction (HMW-Fg). The concentration of HMW-Fg increased continuously, and at 20 h reached values higher than those obtained from normal plasma. HMW-Fg represented about 95% of the total fibrinogen during the first 35 h. The degree of phosphorylation of patient fibrinogen increased from 30% before treatment to 65% during the first 5 h, and then slowly declined to 50% at 35 h.The early rates of fibrinopeptide A (FPA) and phosphorylated fibrinopeptide A (FPAp) release are higher in patient fibrinogen than in isolated normal HMW-Fg and normal fibrinogen after thrombin addition. The early rate of fibrinopeptide B (FPB) release is the same for the three fibrinogen groups. However, the late rate of FPB release is higher in patient fibrinogen than in normal HMW-Fg and normal fibrinogen. Therefore, the newly synthesized fibrinogen clots faster than fibrinogen in the normal steady state.In two of the 15 patients who had occluded coronary arteries after SK treatment the HMW-Fg and FPAp levels increased as compared with the 13 patients who had patent coronary arteries.These results provide some support for the idea that an increased synthesis of fibrinogen in circulation may result in a procoagulant tendency. If this is so, the HMW-Fg and FPAp content may serve as a risk index for thrombosis.

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