Main Menu

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.

Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and is associated with nearly 200,000 cancers and 140,000 deaths each year. EBV-associated cancers include Hodgkin's lymphoma, non-Hodgkin's lymphoma, Burkitt B cell lymphoma, and EBV post-transplant lymphoproliferative disease. The latent reservoir for EBV in the body is the B lymphocyte. Thus, blocking B cell infection is important for reducing EBV-related disease.

Flaviviruses such as Zika virus, dengue virus, West Nile virus, yellow fever virus, and Japanese encephalitis virus cause widespread illness and death throughout the world. Typically, flaviviruses get transmitted through the bite of infected mosquitoes and ticks.

RSV is the most important viral agent of severe respiratory disease in infants and young children worldwide and also causes substantial morbidity and mortality in older adults. RSV is estimated to cause more than 33 million lower respiratory tract illnesses, three million hospitalizations, and nearly 200,000 childhood deaths worldwide annually, with many deaths occurring in developing countries. However, despite the prevalence of RSV and the dangers associated with infection, no RSV vaccine has been successfully developed to date.

According to the World Health Organization (WHO), rabies causes greater than 59,000 deaths every year in over 150 countries as of 2017. A rapid and reliable diagnostic test for rabies is critical for prophylaxis considerations in humans bitten by animals as well as for basic surveillance and animal rabies control programs. The World Organization of Animal Health (OIE) and WHO Expert Committee on Rabies recently approved the direct rapid immunohistochemical test (DRIT) for rabies diagnostics.

CDC and collaborating researchers have developed a new monoclonal antibody that recognizes canine IgG (likely IgG4 subclass). This anti-dog IgG reagent could be used to detect antibody reactions to a variety of antigens and has potential use in a wide variety of diagnostic or research applications.

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.

Rotaviruses cause severe gastroenteritis in humans and animals globally. Currently, there are eight known serogroups (A-H) of rotaviruses. Group C rotavirus (GpC RV) causes sporadic cases and outbreaks of acute diarrhea in children and adults worldwide. GpC RV is also associated with diarrhea in swine. Currently, no simple and reliable diagnostic test exists for GpC RV, so disease prevalence remains unknown.

Vaccines for SARS-CoV-2 are increasingly available under emergency use authorizations; however, indications are currently limited to individuals twelve (12) years or older. They also involve intramuscular immunization, which does not directly stimulate local immunity in the respiratory tract, the primary site of SARS-CoV-2 infection, shedding and spread. While the major burden of COVID-19 disease is in adults, infection and disease also occur in infants and young children, contributing to viral transmission.