The National Institutes of Health National Institute of General Medical Sciences awarded a $903,000 Project Grant to The University of Toledo to develop new glycosylation methods for microbial glycan synthesis under the Biomedical Research and Research Training program (CFDA 93.859). Over a three-year period from September 2022 to August 2025, the University will create two new catalytic glycosylation methodologies - a cationic gold(I)-catalyzed glycosylation using glycosyl...
This federal Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), part of the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $247,750 to support structural investigations of the SARS-CoV-2 spike protein. The research aims to characterize how glycosylation (the addition of sugar molecules) of the spike protein affects its structure and function, which is critical for virus entry and immune system interactions. This research will...
This Project Grant award, valued at $792,687.00 and issued by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), supports research to define the structural features of sialoglycans necessary for influenza A virus (IAV) infection and adaptation across various host species. The key activities under this award include: 1) using CRISPR/Cas9 techniques to truncate different types of sialoglycans in human lung...
The National Institute of General Medical Sciences (NIGMS) awarded a 5-year, $363,177 Project Grant under the Biomedical Research and Research Training program (CFDA 93.859) to the West Virginia University Research Corporation. The grant supports the development of novel nanogel electrophoresis technologies to advance the analysis and synthesis of glycosylated biomolecules. Key objectives include: Creating rapid, low-volume assays to quantify enzyme activity and characterize...
This $1,000,000 Cooperative Agreement awarded by the National Science Foundation (NSF) under the Technology, Innovation, and Partnerships (TIP) program (CFDA 47.084) supports research and development efforts by Akanocure Pharmaceuticals Inc. to optimize a novel, broad-spectrum antiviral and immunomodulatory agent for oral administration against coronaviruses. The project focuses on lead optimization, including the design, synthesis, and testing of analogs with improved drug-like properties for...
This Project Grant award from the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training (CFDA 93.859) program, provides $1,640,169 to Synvivia, Inc. to validate a platform for identifying cyclic peptides that can dramatically increase the yield and quality of adeno-associated virus (AAV) vectors manufactured for gene therapy. The key objectives are to: 1) demonstrate that Synvivia's cyclic peptide discovery library contains peptides that...
This Project Grant award of $408,007 from the National Science Foundation (NSF) Engineering program (CFDA 47.041) aims to develop a technology called "glycosequencing" that uses next-generation sequencing (NGS) to sequence and quantify glycan structures. The project will first identify an optimal set of lectins, biochemically characterize them, and prepare lectin barcoding for NGS. It will also build a training dataset using recombinant proteins produced in glycoengineered Chinese...
This $477,226 federal Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) aims to discover novel antiviral systems in microbial eukaryotes. The research will focus on understanding how the amoeba genus Acanthamoeba defends against giant viruses called Megavirales, and then expand that knowledge to other microbial eukaryotes. The project will leverage cutting-edge AI techniques and...
The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $626,423 Project Grant under the Allergy and Infectious Diseases Research program (CFDA 93.855) to the University of Texas Medical Branch at Galveston (UTMB). The funding will support research to explore the dependence of arenaviruses on the metabolism of the monosaccharides D-glucose and D-mannose, with the goal of developing carbohydrate antimetabolite compounds as potential pan-arenavirus therapeutics. Specifically,...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $847,141 to investigate the role of HIV-1 integrase (IN) in virion morphogenesis and target it with novel allosteric integrase inhibitors. The research aims to delineate the sequence and structural features of viral RNA recognized by HIV-1 IN and determine cryo-EM structures of IN tetramers bound to cognate viral RNA...
ACTIVATED SUGARS, OLIGOSACCHARIDES AND GLYCANS FOR ANTIVIRAL RESEARCH - 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.