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Streptococcus pneumoniae (S. pneumoniae) bacteria, or pneumococcus, can cause many types of illnesses. These range from ear and sinus infections to life-threatening conditions such as pneumonia, bloodstream infections, and meningitis. Pneumococci are surrounded by a polysaccharide capsule, which is thought to help it evade the immune system. Presently, over 90 known serotypes of S. pneumoniae have been identified, of which only a minority produce the majority of pneumococcal infections; a serotype is defined by a unique pneumococcal capsule structure.

Scrub typhus is a bacterial disease caused by Orientia tsutsugamushi (O. tsutsugamushi or Ots) that is spread to people through bites of infected chiggers (larval mites). The most common symptoms can include fever, headache, body aches, and sometimes rash. Severe illness can lead to organ failure and bleeding which can be fatal if left untreated. Most cases of scrub typhus occur in Asia Pacific countries, however, recent reports document establishment in the Arabian Peninsula, Chile, and possibly Kenya.

Chemokine receptors are expressed by many cells, including lymphoid cells, and function to mediate cell trafficking and localization. CC chemokine receptor 5 (CCR5) is a seven-transmembrane, G protein-coupled receptor (GPCR) which regulates trafficking and effector functions of memory/effector T-lymphocytes, macrophages, and immature dendritic cells. Chemokine binding to CCR5 leads to cellular activation through pertussis toxin-sensitive heterotrimeric G proteins as well as G protein-independent signalling pathways.

Clinical and biological specimens often contain microbial nucleic acid in extremely low quantities, presenting a significant challenge for the detection of viral and bacterial pathogens. This also prevents direct sequencing of non-culturable samples using next-generation sequencing (NGS). Currently, NGS library preparation on most platforms requires 0.1 ng to 10 µg of DNA or cDNA, while microbial or viral nucleic acids in clinically relevant specimens, such as blood, serum, respiratory secretions, cerebral spinal fluid, and stool, often contain less than 0.1 ng.

These small molecules are novel nucleotide derivatives, containing either a purine or pyrimidine nucleobase, that competitively block the enzyme CD73, also known as ecto-5'-nucleotidase. This enzyme converts extracellular AMP (not a potent activator of adenosine receptors) to adenosine (the native activator of 4 subtypes of adenosine receptors. CD73 inhibitors are being used, in clinical trials and preclinical research, in conjunction with cancer immunotherapy.

Respiratory Syncytial Virus (RSV) infects nearly all children by their second birthday. RSV usually causes mild respiratory illness, however, a subset of patients experience severe infection that require hospitalization. Successful host defense against viral pathogens requires rapid recognition of the virus and activation of both innate and adaptive immunity. Toll-Like Receptors (TLRs) are responsible for mounting an innate immune response and genetic variations within TLRs modulate severity of infection.

Anthrax, whether resulting from natural or bioterrorist-associated exposure, is a constant threat to human health. Bacillus anthracis is the causative agent of anthrax. It is surrounded by a polypeptide capsule of poly-gamma-D-glutamic acid (gamma-D-PGA), which is essential for virulence, is poorly immunogenic and has anti-phagocytic properties. Antibodies to the capsule have been shown to enhance phagocytosis and killing of encapsulated bacilli.

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.

Simian T-cell lymphotropic viruses (STLV) are nonhuman primate retroviruses closely related to the human T-lymphotropic virus (HTLV). Types I, II, and III of HTLV have been found in humans and are believed to have originated from cross-species transmission of STLV from infected nonhuman primates. The HTLV viruses are known to cause leukemia, lymphoma, and neurological disorders.

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.