According to 2010-2014 World Health Organization (WHO) research, dog-transmitted human rabies was present or suspected in 150 countries and territories worldwide. Domestic dogs were the most common reservoir of the rabies virus in these countries, and more than 99% of human deaths were caused by dog-transmitted rabies. Rabies is 100% preventable in dogs with appropriate administration of vaccines.

Zika virus infection during pregnancy can cause microcephaly and other severe birth defects. The CDC Zika MAC-ELISA (IgM antibody capture enzyme-linked immunosorbent assay) currently used for diagnosis detects antibodies produced to fight a Zika virus infection. However, reactivity of flavivirus antibodies (from exposure to other mosquito-borne infections such as dengue or West Nile virus) can complicate the interpretation of these results.

The U.S. Food and Drug Administration and World Health Organization (WHO) approved the antiretroviral drug emtricitabine (FTC)/ tenofovir disoproxil fumurate (TDF) combination for HIV pre-exposure prophylaxis (PrEP) in high risk populations. Efficacy of PrEP depends strongly on adherence to taking the FTC/TDF pill daily. In the US, the Centers for Disease Control and Prevention (CDC) estimates that 1.2 million Americans will benefit from PrEP. FTC is also a key component of antiretroviral therapy (ART) regimens of HIV-infected persons and significantly associated with adherence.

Following primary dengue virus (DENV) infection, non-structural protein 1 (NS1), a dengue-specific glycoprotein, is present in blood and is easily detected by various assays. However, for any infection thereafter (secondary infection), bioavailability of the glycoprotein greatly reduces sensitivity of DENV detection. Since secondary DENV infection is a risk factor for developing hemorrhagic fever, there is increasing need for more sensitive detection at this stage.

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.

Monoclonal antibodies (mAbs) have become a mainstay of therapy for many cancers. However, antibody therapy is not completely effective in some applications due to loss of the target surface antigen on cancer cells. Such mAb-induced “escape variants” are no longer sensitive to the therapeutic mAb therapy. It was observed that the escape variants carried covalently bound complement activation fragments, especially C3d. NIH inventors have generated several C3d-specific mouse and rabbit monoclonal antibodies to re-target cells that have escaped from mAb therapy.

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.

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.

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.