Targeting eEF1A reprograms translation and uncovers broad-spectrum antivirals against cap or mA protein synthesis routes.

Plitidepsin is an antitumoral compound safe for treating COVID-19 that targets the translation elongation factor eEF1A. Here we detect that plitidepsin decreases de novo cap-dependent translation of SARS-CoV-2 and non-viral RNAs but affects less than 13% of the host proteome, thus preserving cellular viability. In response to plitidepsin, cells upregulate EIF2AK3 and proteins that reduce translation, but also proteins that support proteostasis via ribosome synthesis and cap-independent translation by eIF4G2 and IGF2BP2.

Randomized Controlled Trial Substudy of Cell-specific Mechanisms of Janus Kinase 1 Inhibition With Upadacitinib in the Crohn's Disease Intestinal Mucosa: Analysis From the CELEST Study.

Background: Janus kinase (JAK) inhibition shows promise for treatment of patients with moderate to severe Crohn's disease. We aimed to provide mechanistic insights into the JAK1-selective inhibitor upadacitinib through a transcriptomics substudy on biopsies from patients with Crohn's disease from CELEST.

Methods: Seventy-four patients consented to this optional substudy.

Multi-omic modelling of inflammatory bowel disease with regularized canonical correlation analysis.

Background: Personalized medicine requires finding relationships between variables that influence a patient's phenotype and predicting an outcome. Sparse generalized canonical correlation analysis identifies relationships between different groups of variables. This method requires establishing a model of the expected interaction between those variables.