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Principal Investigator: Leila Aminova
Organization: MIDWEST BIOPROCESSING CENTER, LLC
Fiscal Year: 2021
Award: $982,971
Funding agency: National Institute of General Medical Sciences
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.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><ACE2><Acylneuraminyl hydrolase><Adhesions><Anti-Infective Agents><Anti-Infective Drugs><Anti-Infectives><Anti-infective Preparation><AntiInfective Drugs><AntiInfectives><Antigenic Determinants><Antiinfective Agents><Antiviral Agents><Antiviral Drugs><Antivirals><Binding><Binding Determinants><Biology><Bioreactors><Breast Milk><Breastmilk><CMP Acetylneuraminic Acid><CMP-NANA><CMP-Sialic Acid><COVID-19 virus><COVID19 virus><Candida><Catalogs><Cell Body><Cells><Clinical><CoV-2><CoV2><Complex><Custom><Cytidine Monophosphate N-Acetylneuraminic Acid><D pneumoniae><D-Galactoside-Binding Lectin><D-Glucose><D-Mannose><D. pneumoniae><Dengue><Deoxygalactose><Development><Development and Research><Dextrose><Diplococcus pneumoniae><Directed Molecular Evolution><Engineering><Enzyme Gene><Enzymes><Epitopes><Feasibility Studies><Fucose><GDP Fucose><GDP Mannose><Galactose Binding Lectin><Galaptins><Galectins><Glucose><Glycans><Glycobiology><Glycoproteins><Goals><Grant><Guanosine 5'-(trihydrogen diphosphate), P'-(6-deoxy-beta-L-galactopyranosyl) ester><Guanosine Diphosphate Fucose><Guanosine Diphosphate Mannose><Guanosine Diphosphofucose><Guanosine Diphosphomannose><Guanosine Pyrophosphate Mannose><H influenzae type b><H. influenzae type b><HCV infection><HIV Infections><HTLV-III Infections><HTLV-III-LAV Infections><Haemophilus influenzae type b><Hepatitis C><Hepatitis C virus infection><Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted><Hepatitus C><Hib><Human><Human Milk><Human Mother's Milk><Human T-Lymphotropic Virus Type III Infections><Immunity><Infection><Innate Immunity><Investigators><Link><Mammary Gland Milk><Mannopyranose><Mannopyranoside><Mannose><Masks><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Meningococcus><Metabolic Glycosylation><Methods><Modeling><Modern Man><Molecular Interaction><Monilia><Mother's Milk><N meningitidis><N-Acetylneuraminic Acids><N-Acylneuraminate Glycohydrolases><N. meningitidis><Native Immunity><Natural Immunity><Nature><Neisseria meningitidis><Neuraminidase><Non-Specific Immunity><Nonspecific Immunity><Oligosaccharide Sialidase><Oligosaccharides><Parasites><Pathology><Phase><Plasmodium><Play><Pneumococcus><Polysaccharides><Price><Production><Property><Protein Glycosylation><Proteins><R & D><R&D><Reagent><Receptor Protein><Research><Research Personnel><Research Support><Researchers><Role><S pneumoniae><S-Type Lectins><S. pneumoniae><SARS corona virus 2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Sialic Acids><Sialidase><Streptococcus pneumoniae><Surface Proteins><System><T-Cells><T-Lymphocyte><Technology><Therapeutic><UDP Galactose><UDPGal><Uridine Diphosphate Galactose><Uridine Diphosphogalactose><Uridine Pyrophosphogalactose><Vaccine Research><Vaccines><Viral><Viral Receptor><Virus><Virus Receptors><Work><Wuhan coronavirus><alpha-Fucose><angiotensin converting enzyme 2><angiotensin converting enzyme II><anti-viral agents><anti-viral drugs><anti-virals><assay development><bacteria pathogen><bacterial pathogen><beta CoV><beta coronavirus><beta-D-Galactosyl-Specific Lectin><beta-Galactoside Binding Lectin><betaCoV><betacoronavirus><catalog><chitobiose><communicable disease control agent><coronavirus disease 2019 virus><developmental><directed evolution><exo alpha sialidase><feasibility research><fungus><galactokinase><glycosylation><hCoV19><hep C><hepatitis non A non B><inhibitor><inhibitor/antagonist><large scale production><maternal milk><nCoV2><new drug treatments><new drugs><new therapeutics><new therapy><next generation therapeutics><non A, non B hepatitis><non-A, non-B hepatitis><novel><novel drug treatments><novel drugs><novel therapeutics><novel therapy><pathogenic bacteria><pricing><receptor><research and development><scale up><social role><stem><success><sugar><sugar nucleotide><thermolability><thermostability><thymus derived lymphocyte><β CoV><β coronavirus><βCoV>