TRUEE - unfolding software

TRUEE (Time-dependent Regularized Unfolding for Economics and Engineerings) is a new unfolding program, written in C++. TRUEE is based on the RUN algorithm [1] and is intended to be an universal tool for the solution of inverse problems in physics as well as in other fields as economics, where inverse problems are not yet sufficiently investigated. The current status of the software and long-term objectives are described

Providing Information by Resource- Constrained Data Analysis

The Collaborative Research Center SFB 876 (Providing Information by Resource-Constrained Data Analysis) brings together the research fields of data analysis (Data Mining, Knowledge Discovery in Data Bases, Machine Learning, Statistics) and embedded systems and enhances their methods such that information from distributed, dynamic masses of data becomes available anytime and anywhere. The research center approaches these problems with new algorithms respecting the resource constraints in the different scenarios. This Technical Report presents the work of the members of the integrated graduate school

Repurposing screen identifies novel candidates for broad-spectrum coronavirus antivirals and druggable host targets

Libraries composed of licensed drugs represent a vast repertoire of molecules modulating physiological processes in humans, providing unique opportunities for the discovery of host-targeting antivirals. We screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) repurposing library with approximately 12,000 molecules for broad-spectrum coronavirus antivirals and discovered 134 compounds inhibiting an alphacoronavirus and mapping to 58 molecular target categories. Dominant targets included the 5-hydroxytryptamine receptor, the dopamine receptor, and cyclin-dependent kinases. Gene knock-out of the drugs’ host targets including cathepsin B and L (CTSB/L; VBY-825), the aryl hydrocarbon receptor (AHR; Phortress), the farnesyl-diphosphate farnesyltransferase 1 (FDFT1; P-3622), and the kelch-like ECH-associated protein 1 (KEAP1; Omaveloxolone), significantly modulated HCoV-229E infection, providing evidence that these compounds inhibited the virus through acting on their respective host targets. Counter-screening of all 134 primary compound candidates with SARS-CoV-2 and validation in primary cells identified Phortress, an AHR activating ligand, P-3622-targeting FDFT1, and Omaveloxolone, which activates the NFE2-like bZIP transcription factor 2 (NFE2L2) by liberating it from its endogenous inhibitor KEAP1, as antiviral candidates for both an Alpha- and a Betacoronavirus. This study provides an overview of HCoV-229E repurposing candidates and reveals novel potentially druggable viral host dependency factors hijacked by diverse coronaviruses