The Experts below are selected from a list of 84777 Experts worldwide ranked by ideXlab platform
Rainer Haag - One of the best experts on this subject based on the ideXlab platform.
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Spiky Nanostructures with Geometry-matching Topography for Virus Inhibition.
Nano letters, 2020Co-Authors: Chuanxiong Nie, Chong Cheng, Marlena Stadtmüller, Hua Yang, Yi Xia, Thorsten Wolff, Rainer HaagAbstract:Geometry-matching has been known to benefit the formation of stable biological interactions in natural systems. Herein, we report that the spiky nanostructures with matched topography to the influenza A Virus (IAV) virions could be used to design next-generation advanced Virus inhibitors. We demonstrated that nanostructures with spikes between 5 and 10 nm bind significantly better to virions than smooth nanoparticles, due to the short spikes inserting into the gaps of glycoproteins of the IAV virion. Furthermore, an erythrocyte membrane (EM) was coated to target the IAV, and the obtained EM-coated nanostructures could efficiently prevent IAV virion binding to the cells and inhibit subsequent infection. In a postinfection study, the EM-coated nanostructures reduced >99.9% Virus replication at the cellular nontoxic dosage. We predict that such a combination of geometry-matching topography and cellular membrane coating will also push forward the development of nanoinhibitors for other Virus strains, including SARS-CoV-2.
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Multivalent Peptide–Nanoparticle Conjugates for Influenza-Virus Inhibition
Angewandte Chemie (International ed. in English), 2017Co-Authors: Daniel Lauster, Kai Ludwig, Christoph Böttcher, Rainer Haag, Maria Glanz, Markus Bardua, Markus Hellmund, Ute Hoffmann, Alf Hamann, Christian P. R. HackenbergerAbstract:To inhibit binding of the influenza A Virus to the host cell glycocalyx, we generate multivalent peptide–polymer nanoparticles binding with nanomolar affinity to the Virus via its spike protein hemagglutinin. The chosen dendritic polyglycerol scaffolds are highly biocompatible and well suited for a multivalent presentation. We could demonstrate in vitro that by increasing the size of the polymer scaffold and adjusting the peptide density, viral infection is drastically reduced. Such a peptide–polymer conjugate qualified also in an in vivo infection scenario. With this study we introduce the first non-carbohydrate-based, covalently linked, multivalent Virus inhibitor in the nano- to picomolar range by ensuring low peptide-ligand density on a larger dendritic scaffold.
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Virus Inhibition induced by polyvalent nanoparticles of different sizes
Nanoscale, 2014Co-Authors: Jonathan Vonnemann, Christian Sieben, Christopher Wolff, Kai Ludwig, Christoph Böttcher, Andreas Herrmann, Rainer HaagAbstract:The development of antiviral agents is one of the major challenges in medical science. So far, small monovalent molecular drugs that inhibit the late steps in the viral replication cycle, i.e., Virus budding, have not worked well which emphasizes the need for alternative approaches. Polyvalently presented viral receptors, however, show potential as good inhibitors of Virus–cell binding, which is the first step in the viral infection cycle. By gradually increasing the size of ligand functionalized gold nanoparticles, up to Virus-like dimensions, we are now able to quantify the polyvalent enhancement of Virus–cell binding Inhibition and to identify varying mechanisms of Virus Inhibition with different efficacies: by employing a new binding assay we found that surface area-normalized polysulfated gold nanoparticles of diameters equal to and larger than the Virus diameter (>50 nm) more efficiently inhibit the binding of vesicular stomatitis Virus (VSV) to cells than smaller particles. On a per particle basis, larger sized gold nanoparticles were surprisingly shown to inhibit the viral infection up to two orders of magnitude more efficiently than smaller particles, which suggests different mechanisms of Virus Inhibition. Based on complementary electron microscopic data, we noticed that larger gold nanoparticles act as efficient cross-linkers between virions, whereas smaller gold nanoparticles decorate the surface of individual Virus particles. Our systematic study accentuates the need for the design of biodegradable, Virus-sized inhibitors capitalizing on polyvalent binding.
Lauren R. Blankenship - One of the best experts on this subject based on the ideXlab platform.
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A Quick Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors*.
ChemMedChem, 2020Co-Authors: Kai S. Yang, Xinyu R., Yugendar R. Alugubelli, Danielle A. Scott, Erol C. Vatansever, Aleksandra Drelich, Banumathi Sankaran, Zhi Z. Geng, Lauren R. BlankenshipAbstract:The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro ) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the Virus from replicating in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1MPro ), we have designed and synthesized a series of SC2MPro inhibitors that contain s-(S-2-oxopyrrolidin-3-yl)-alaninal (Opal) for the formation of a reversible covalent bond with the SC2MPro active-site cysteine C145. All inhibitors display high potency with Ki values at or below 100â nM. The most potent compound, MPI3, has as a Ki value of 8.3â nM. Crystallographic analyses of SC2MPro bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus Inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS-CoV-2-induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS-CoV-2-induced cytopathogenic effect in Vero E6 cells at 2.5-5â µM and A549/ACE2 cells at 0.16-0.31â µM. Their Virus Inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID-19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2MPro inhibitors with ultra-high antiviral potency.
Chuanxiong Nie - One of the best experts on this subject based on the ideXlab platform.
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Spiky nanostructures for Virus Inhibition and infection prevention
Smart materials in medicine, 2020Co-Authors: Chuanxiong Nie, Hongrong Luo, Jinku Bao, Chong ChengAbstract:Abstract The outbreak of a novel highly infectious Virus, severe acute respiratory syndrome coronaVirus 2 (SARS-CoV-2), has aroused people’s concern about public health. The lack of ready-to-use vaccines and therapeutics makes the fight with these pathogens extremely difficult. To this point, rationally designed Virus entry inhibitors that block the viral interaction with its receptor can be novel strategies to prevent Virus infection. For ideal Inhibition of the Virus, the Virus-inhibitor interaction has to outperform the Virus-host interaction. In our view, the morphology of the inhibitor should be carefully designed to benefit Virus-inhibitor binding, especially that the surfaces of Viruses are mostly rough due to the existence of surface proteins for receptor-binding. In this perspective article, we would like to discuss the recent progress of designing inhibitors with spiky topography to maximize the interactions between Viruses and inhibitors. We also would like to share our idea for the future study of inhibitors to prevent Virus infection.
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Spiky Nanostructures with Geometry-matching Topography for Virus Inhibition.
Nano letters, 2020Co-Authors: Chuanxiong Nie, Chong Cheng, Marlena Stadtmüller, Hua Yang, Yi Xia, Thorsten Wolff, Rainer HaagAbstract:Geometry-matching has been known to benefit the formation of stable biological interactions in natural systems. Herein, we report that the spiky nanostructures with matched topography to the influenza A Virus (IAV) virions could be used to design next-generation advanced Virus inhibitors. We demonstrated that nanostructures with spikes between 5 and 10 nm bind significantly better to virions than smooth nanoparticles, due to the short spikes inserting into the gaps of glycoproteins of the IAV virion. Furthermore, an erythrocyte membrane (EM) was coated to target the IAV, and the obtained EM-coated nanostructures could efficiently prevent IAV virion binding to the cells and inhibit subsequent infection. In a postinfection study, the EM-coated nanostructures reduced >99.9% Virus replication at the cellular nontoxic dosage. We predict that such a combination of geometry-matching topography and cellular membrane coating will also push forward the development of nanoinhibitors for other Virus strains, including SARS-CoV-2.
Chong Cheng - One of the best experts on this subject based on the ideXlab platform.
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Spiky nanostructures for Virus Inhibition and infection prevention
Smart materials in medicine, 2020Co-Authors: Chuanxiong Nie, Hongrong Luo, Jinku Bao, Chong ChengAbstract:Abstract The outbreak of a novel highly infectious Virus, severe acute respiratory syndrome coronaVirus 2 (SARS-CoV-2), has aroused people’s concern about public health. The lack of ready-to-use vaccines and therapeutics makes the fight with these pathogens extremely difficult. To this point, rationally designed Virus entry inhibitors that block the viral interaction with its receptor can be novel strategies to prevent Virus infection. For ideal Inhibition of the Virus, the Virus-inhibitor interaction has to outperform the Virus-host interaction. In our view, the morphology of the inhibitor should be carefully designed to benefit Virus-inhibitor binding, especially that the surfaces of Viruses are mostly rough due to the existence of surface proteins for receptor-binding. In this perspective article, we would like to discuss the recent progress of designing inhibitors with spiky topography to maximize the interactions between Viruses and inhibitors. We also would like to share our idea for the future study of inhibitors to prevent Virus infection.
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Spiky Nanostructures with Geometry-matching Topography for Virus Inhibition.
Nano letters, 2020Co-Authors: Chuanxiong Nie, Chong Cheng, Marlena Stadtmüller, Hua Yang, Yi Xia, Thorsten Wolff, Rainer HaagAbstract:Geometry-matching has been known to benefit the formation of stable biological interactions in natural systems. Herein, we report that the spiky nanostructures with matched topography to the influenza A Virus (IAV) virions could be used to design next-generation advanced Virus inhibitors. We demonstrated that nanostructures with spikes between 5 and 10 nm bind significantly better to virions than smooth nanoparticles, due to the short spikes inserting into the gaps of glycoproteins of the IAV virion. Furthermore, an erythrocyte membrane (EM) was coated to target the IAV, and the obtained EM-coated nanostructures could efficiently prevent IAV virion binding to the cells and inhibit subsequent infection. In a postinfection study, the EM-coated nanostructures reduced >99.9% Virus replication at the cellular nontoxic dosage. We predict that such a combination of geometry-matching topography and cellular membrane coating will also push forward the development of nanoinhibitors for other Virus strains, including SARS-CoV-2.
Elizabeth A. Mcgraw - One of the best experts on this subject based on the ideXlab platform.
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Wolbachia-Based Dengue Virus Inhibition Is Not Tissue-Specific in Aedes aegypti.
PLoS neglected tropical diseases, 2016Co-Authors: Hilaria E. Amuzu, Elizabeth A. McgrawAbstract:Background Dengue fever, caused by the dengue Virus (DENV), is now the most common arboVirus transmitted disease globally. One novel approach to control DENV is to use the endosymbiotic bacterium, Wolbachia pipientis, to limit DENV replication inside the primary mosquito vector, Aedes aegypti. Wolbachia that is naturally present in a range of insects reduces the capacity for Viruses, bacteria, parasites and fungi to replicate inside insects. Wolbachia’s mode of action is not well understood but may involve components of immune activation or competition with pathogens for limited host resources. The strength of Wolbachia-based anti DENV effects appear to correlate with bacterial density in the whole insect and in cell culture. Here we aimed to determine whether particular tissues, especially those with high Wolbachia densities or immune activity, play a greater role in mediating the anti DENV effect. Methodology/findings Ae. aegypti mosquito lines with and without Wolbachia (Wildtype) were orally fed DENV 3 and their viral loads subsequently measured over two time points post infection in the midgut, head, salivary glands, Malpighian tubules, fat body and carcass. We did not find correlations between Wolbachia densities and DENV loads in any tissue, nor with DENV loads in salivary glands, the endpoint of infection. This is in contrast with strong positive correlations between DENV loads in a range of tissues and salivary gland loads for Wildtype mosquitoes. Lastly, there was no evidence of a heightened role for tissues with known immune function including the fat body and the Malpighian tubules in Wolbachia’s limitation of DENV. Conclusion/significance We conclude that the efficacy of DENV blocking in Wolbachia infected mosquitoes is not reliant on any particular tissue. This work therefore suggests that the mechanism of Wolbachia-based antiviral effects is either systemic or acts locally via processes that are fundamental to diverse cell types. We further conclude that the relationship between DENV blocking and Wolbachia density is not linear in mosquito tissues
