Provided herein is a method of identifying a compound that induces the formation of Hepatitis B Virus (HBV) aberrant viral capsid structures.

This disclosure relates to the surprising and unexpected finding that the well-known cancer protein, Myeloid Cell Leukemia-1 (MCL-1), binds to and modulates the enzymatic activity of Very Long Chain Acyl CoA Dehydrogenase (VLCAD), thereby regulating fatty acid β-oxidation. This finding is employed in compositions and methods of treating cancer, metabolic diseases, or other conditions characterized by excessive fatty acid β-oxidation by blocking or reducing the energy production of cells (e.g., cancer) through inhibiting the MCL-1/VLCAD interaction and/or directly inhibiting VLCAD enzymatic activity. In addition, the disclosure features methods for identifying such agents that inhibit the interaction between MCL-1 and VLCAD or that inhibit VLCAD enzymatic activity.

Disclosed herein are methods, compositions, systems, and kits related to functional testing of soluble polypeptides in a single-cell format.

The invention is in the field of therapy of gut inflammatory diseases such as Inflammatory Bowel Diseases (IBD) or Irritable Bowel Syndrome (IBS) including Gluten hypersensitivity. The inventors showed that ELA2A secreted by epithelial cells in the extracellular space is over-expressed in IBD conditions degrading tight junction proteins and controlling cytokines expression. Overexpression of ELA2A conferred a pro-inflammatory phenotype both in cell expression systems and in vivo in animal model of IBD. The inventors also showed that ELA2 over-expressing intestinal epithelial cells increase the release of CXCL8 protein compared to control cells. The increased CXCL-8 protein release observed in cells overexpressing ELA2A is inhibited by ELAFIN addition to the culture, in a dose-dependent manner. In particular, the invention relates to inhibitors of Elastase ELA2A, for use in the treatment of Inflammatory Bowel Diseases, such as Crohn's Disease, Ulcerative Colitis, Celiac disease, and Pouchitis.

The disclosure provides polypeptides comprising an engineered p27, or a fragment thereof. Such polypeptides may be used to form trimeric protein complexes with a cyclin-dependent kinase 4 (Cdk4) (or a variant thereof) or Cdk6 (or a variant thereof), and a cyclin D (CycD) or a variant thereof.

Based on the discovery that MBLAC1 is a specific, high-affinity target for Ceftriaxone (Cef), MBLAC1 may be used for identifying treatments for addiction to substances of abuse. Methods for identifying therapeutic agents for treatment of addiction to a substance of abuse include using an assay to determine if a test agent is capable of binding to MBLAC1 or disrupting binding between MBLAC1 protein and Cef, and identifying such a test agent as a candidate therapeutic agent for treatment of addiction to a substance of abuse. MBLAC knock-out (KO) animals, methods of use thereof, and kits are used for identifying a therapeutic agent that reduces the actions of at least one substance of abuse. Methods also include using cellular extracts from tissue or cultured cells taken from wild-type (WT) MBLAC1 and MBLAC1 KO animals for screening for novel, Cef-like molecules in vitro, and using cells from a MBLAC1 KO animal to test for Cef-like actions of a test molecule.

Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

The present disclosure provides a method and a platform for enhancing detection activity of an interaction between a spike protein receptor binding domain of coronavirus from a specimen and a human angiotensin-converting enzyme II. The method and the platform of the present disclosure use a cleavable luciferase as a report test for the combination of the spike protein receptor binding domain of coronavirus (such as novel coronavirus) and angiotensin-converting enzyme II. Screening is carried out at the cellular level. The strength of the drug's influence on the interaction between the two molecules can be judged by the strength of the luminescence signal. The detection time can be completed within 20 minutes.

A method for determining activity of an acyl transferase enzyme, the method comprising: (i) preparing a reaction mixture comprising: (a) an acyl transferase enzyme, (b) a peptide substrate bound to a fluorophore, wherein the substrate is a cysteine-containing oligopeptide of 5-25 amino acids in length, (c) an acyl-CoA, and (d) a detergent comprising micelles, wherein the acyl transferase enzyme mediates acylation on a cysteine of said peptide substrate to result in association of the peptide with micelles of the detergent with resultant increase in fluorescence polarization; and (ii) measuring fluorescent signal of the reaction mixture; wherein an increase in fluorescence polarization of the reaction mixture compared to fluorescence polarization of a control reaction indicates acyl transferase activity of the acyl transferase enzyme. The above assay method may also be used for screening compounds for their ability to act as inhibitors of an acyl transferase enzyme.

Mutant mono ADP-ribose-polymerases (mono-PARP) proteins and small molecule compound substrates specific for the mutant mono-PARP proteins as well as methods of using these compositions to identify protein targets of the mono-PARPs and to screen for antagonists of the mono-PARPs are described.