A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins.

Target class-focused drug discovery has a strong track record in pharmaceutical research, yet public domain data indicate that many members of protein families remain unliganded. Here we present a systematic approach to scale up the discovery and characterization of small molecule ligands for the WD40 repeat (WDR) protein family. We developed a comprehensive suite of protocols for protein production, crystallography, and biophysical, biochemical, and cellular assays.

ASPEN international survey on ethical competencies dealing with decision-making in the use of artificially administered nutrition and hydration and competency application in clinical practice.

Background: Ethical competencies dealing with decision-making for clinicians involved in artificially administered nutrition and hydration (AANH) have not been defined in the literature. Although clinical assessments identify nutrition needs and appropriate routes of nutrition administration, an assessment of the ethical, cultural, and spiritual implications of the medical nutrition therapy may be overlooked.

Methods: Eleven competency statements were developed by members of two international sections of the American Society for Parenteral and Enteral Nutrition.

Extensive exploration of structure activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment merging and active learning.

The macrodomain contained in the SARS-CoV-2 non-structural protein 3 (NSP3) is required for viral pathogenesis and lethality. Inhibitors that block the macrodomain could be a new therapeutic strategy for viral suppression. We previously performed a large-scale X-ray crystallography-based fragment screen and discovered a sub-micromolar inhibitor by fragment linking.

Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology: Post Hoc Analysis of the STEP 1, 2, 3, and 5 Trials.

Importance: Obesity is associated with numerous psychosocial complications, making psychiatric safety a consideration for treating people with obesity. Few studies have investigated the psychiatric safety of newly available antiobesity medications.

Objective: To evaluate the psychiatric safety of subcutaneous semaglutide, 2.