Robust proteome profiling of cysteine-reactive fragments using label-free chemoproteomics.

Identifying pharmacological probes for human proteins represents a key opportunity to accelerate the discovery of new therapeutics. High-content screening approaches to expand the ligandable proteome offer the potential to expedite the discovery of novel chemical probes to study protein function. Screening libraries of reactive fragments by chemoproteomics offers a compelling approach to ligand discovery, however, optimising sample throughput, proteomic depth, and data reproducibility remains a key challenge.

Expedited SARS-CoV-2 Main Protease Inhibitor Discovery through Modular 'Direct-to-Biology' Screening.

Reactive fragment (RF) screening has emerged as an efficient method for ligand discovery across the proteome, irrespective of a target's perceived tractability. To date, however, the efficiency of subsequent optimisation campaigns has largely been low-throughput, constrained by the need for synthesis and purification of target compounds. We report an efficient platform for 'direct-to-biology' (D2B) screening of cysteine-targeting chloroacetamide RFs, wherein synthesis is performed in 384-well plates allowing direct assessment in downstream biological assays without purification.

Assessing the impact of COVID-19 on the physical activity of 10-11-year-old children and their parents: Active-6 a mixed-methods study.

Background: Physical activity is essential for long-term health, yet data from before the COVID-19 pandemic showed only 41% of 10- to 11-year-olds met the UK government's physical activity recommendations. Children's physical activity was limited during the national COVID-19 lockdowns. It is important to measure children's physical activity in the recovery period to assess the short- and medium-term impact of the lockdowns.

School-level variation in children's moderate to vigorous intensity physical activity before and after COVID-19: a multilevel model analysis.

Background And Objectives: Schools play a crucial role in facilitating physical activity among children, but the COVID-19 pandemic has affected both children's physical activity and the school environment. It is essential to understand between-school differences in children's physical activity post lockdown, to determine if and how the role of schools has changed.

Design And Participants: Active-6 is a natural experiment comparing postlockdown accelerometer-estimated physical activity to a pre-COVID-19 comparator group.