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Activated Sugars, Oligosaccharides and Glycans for Antiviral Research

用于抗病毒研究的活性糖、低聚糖和聚糖

基本信息

批准号：
10405128
负责人：
Leila Aminova
金额：
$ 86.8万
依托单位：
MIDWEST BIOPROCESSING CENTER, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10405128
关键词：
2019-nCoV ACE2 Adhesions Anti-Infective Agents Antiviral Agents Binding Biology Bioreactors Candida Catalogs Cells Clinical Complex Custom Cytidine Monophosphate N-Acetylneuraminic Acid Dengue Development Directed Molecular Evolution Engineering Enzymes Epitopes Feasibility Studies Fucose Galactose Binding Lectin Glucose Glycobiology Glycoproteins Goals Grant Guanosine Diphosphate Fucose Guanosine Diphosphate Mannose HIV Infections Haemophilus influenzae type b Hepatitis C Human Human Milk Immunity Infection Link Mannose Masks Membrane Proteins Methods Modeling Natural Immunity Nature Neisseria meningitidis Neuraminidase Oligosaccharides Parasites Pathology Phase Plasmodium Play Polysaccharides Price Production Property Protein Glycosylation Proteins Reagent Research Research Personnel Research Support Role Sialic Acids Streptococcus pneumoniae System T-Lymphocyte Technology Uridine Diphosphate Galactose Vaccine Research Vaccines Viral Virus Virus Receptors Work antiviral drug development assay development betacoronavirus chitobiose feasibility research fungus galactokinase glycosylation inhibitor large scale production novel novel therapeutics pathogenic bacteria receptor research and development scale up stem success sugar sugar nucleotide thermostability

项目摘要

SUMMARY The goal of this project is to develop novel methods to produce sugar building blocks, oligosaccharides, and glycans needed to support and grow R&D related to viral glycobiology at large scale and reasonable prices. This technology will support researchers studying viral pathology, analyses of viral binding and interactions with hosts, studies to develop novel antiviral therapeutics and vaccines, and others. Glycobiology is important in a number of ways for viral research. Viral surface proteins are often heavily glycosylated to both avoid recognition by the host cell and, in some cases, interact with host receptors. For example, the spike protein glycosylation of the SARS-CoV-2 virus is usually the extension of an N-linked core pentasaccharide compound, composed of a stem of chitobiose followed by mannoses to form two antennary complexes. Understanding glycosylation of viral spike proteins and their potential epitope masking is of fundamental importance for vaccine research. Receptors recognized by many viruses are glycosylated proteins as well. SARS-CoV-2 and others uses angiotensin-converting enzyme 2, (ACE2) as its receptor, and other b-coronaviruses, utilize sialic acid residues on cellular glycoproteins as receptors. Glycans are currently being studied as vaccines against viruses (Dengue, Hepatitis C), parasites (Plasmodium) and fungi (Candida). Human milk oligosaccharides (HMOs) have been shown to reduce the possibility of infections due to interference with adhesion of pathogenic bacteria and potentially viruses. Galectins have been shown have pro- or anti-viral properties and play important role in innate immunity. Finally, some galectin inhibitors may block HIV infection of T cells. Oligosaccharides are currently isolated from nature or synthesized at extremely low yield via a complex set of protection and deprotection steps. Oligosaccharides and the activated sugar building blocks needed to build them enzymatically are needed in larger quantities to support and spawn additional research in this important field. In the Feasibility study we successfully demonstrated the development of a set of novel enzymes to produce a wide range of key activated sugar building blocks required to build important oligosaccharides. We then demonstrated the use of these activated sugars to extend model oligosaccharide chains. In the Phase II work, we will increase the scale of production of all of these activated sugars, extend the system to produce additional activated sugars needed, and make a number of key oligosaccharides important to viral biology research. Products made during the Phase II Research will be distributed to investigators and in Phase III products will be commercialized as part of our research reagent catalog or by carrying out custom synthesis of oligosaccharides for third parties.

总结