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Niemann-Pick Disease, type C (NPC) is a rare, autosomal recessive, neurodegenerative disease. Approximately 95% of patients with NPC have mutations in NPC1, a gene implicated in intracellular cholesterol trafficking. Mutation of NPC1 causes intracellular accumulation of unesterified cholesterol in late endosomal/lysosomal structures and marked accumulation of glycosphingolipids, especially in neuronal tissue. Thus, NPC patients generally present with hepatosplenomegaly (enlargement of liver and spleen) and neurological degeneration.

The technology describes the composition of small molecule compounds that are antagonists of the P2Y14 receptor. Also provided are methods of using the compounds, including a method of treating a disorder, such as inflammation, diabetes, insulin resistance, hyperglycemia, a lipid disorder, obesity, a condition associated with metabolic syndrome, and asthma, and a method of antagonizing P2Y14 receptor activity in a cell.

The technology discloses composition of compounds that fully antagonize the human P2Y14 receptor, with moderate affinity with insignificant antagonism of other P2Y receptors. Therefore, they are highly selective P2Y14 receptor antagonists. Even though there is no P2Y14 receptor modulators in clinical use currently, selective P2Y14 receptor antagonists are sought as potential therapeutic treatments for asthma, cystic fibrosis, inflammation and possibly diabetes and neurodegeneration.

The coronavirus disease 2019 (COVID-19) is caused by a novel RNA enveloped coronavirus, SARS-CoV-2 when the virus enters human airway cells via an ACE2-mediated entry process. This entry pathway is facilitated by the cell surface heparan sulfate proteoglycan (HSPG), which enhances viral attachment to the cell surface. Researchers at NIDDK and NCATS have discovered a collection of FDA-approved drugs that can interfere with the entry of SARS-CoV-2. These drugs can be grouped into three classes based on the distinct steps in the viral entry pathway that they target.

During lung infection, bloodstream neutrophils (PMNs) responding to infection travel to the airspace lumen. Although successful arrival of microbicidal PMNs to the airspace is essential for host defense against inhaled pathogens, excessive accumulation of PMNs in the lung contributes to the pathogenesis of several prevalent lung disorders, including acute lung injury, bronchiectasis, and COPD. Unfortunately, there is no treatment for controlling PMN accumulation in the lung.

Immunoglobulins play a key role in the immune system. CDC has developed and tested hybridoma cell lines (monoclonal antibody (mAb) clones) for human IgG and other immunoglobulins. The mAbs generated from those hybridomas could be used as a reagent (second Ab) of anti-human immunoglobins in a diagnostic assay for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19 (coronavirus disease 2019) and other assays that detect antigen specific antibodies from human sera.

This technology includes the development and use of small molecule activators of pyruvate kinase (PK) for the treatment of inherited nonspherocytic hemolytic anemia, including PK deficiency. PK deficiency is caused by an inherited deficiency in an enzyme that reduces the lifespan of red blood cells. More than 150 unique mutations have been identified in the PK gene that lead to decreased activity in this essential enzyme in the glycolytic pathway. The prematurely lysed red blood cells can lead to jaundice, splenomegaly, and a hemolytic anemia.

This technology includes the synthesis and use of novel PI3K and HDAC dual inhibitors for the treatment of several cancers. Phosphatidylinositol 3-kinase (PI3K) is activated in many human cancers, and inhibition of these kinases is an established cancer treatment. Histone deacetylases (HDACs) are key regulators of the cell cycle that function through regulating expression of tumor suppressors (p21 and p27), c-Myc and cyclin D1. HDAC inhibition is an emerging therapeutic approach for the treatment of several cancers.

The current invention provides nucleic acid sequences comprising the genomes of infectious hepatitis C viruses (HCV) of genotype 1a and 1b. It covers the use of these sequences, and polypeptides encoded by all or part of the sequences, in the development of vaccines and diagnostic assays for HCV and the development of screening assays for the identification of antiviral agents for HCV.

This technology includes the use of the small molecule metarrestin (ML246) for the treatment of several types of pancreatic cancer. A subcellular structure called the perinucleolar compartment (PNC) is frequently found in metastatic tumors and cancer stem cells. Reduction of PNC prevalence followed by medicinal chemistry was used to identify metarrestin as a compound that reduces PNC prevalence without significantly impacting cell viability. In vitro and in vivo animal work have demonstrated desirable pharmacokinetic properties as well as a reduction in metastatic burden and extended survival.