A combined virtual and nuclear magnetic resonance (NMR)-based screening approach identifies small molecules that bind conserved SARS-CoV-2 RNA structures. Diverse compound libraries are screened usin....

Universität Greifswald

Abstract. La-related proteins (LARPs) are RNA-binding proteins that are involved in a variety of disease-related processes. Most LARPs recognize short sing

Abstract. Recently, a novel tobramycin-responsive riboswitch was developed by a combination of Capture-SELEX and in vivo screening. This riboswitch regulat

We present the development of low molecular weight inhibitors that target the 5′-terminal RNA stem-loop 1 (SL1) of the SARS-CoV-2 genome. SL1 is crucial for allowing viral protein synthesis in the context of global translational repression in infected cells. We applied compound- and RNA-detected nuclear magnetic resonance spectroscopy (NMR) experiments to guide a fragment-growth strategy based on two primary NMR screening hits from a diverse fragment library poised for follow-up chemistry. These primary hits with molecular weights of around 200 Da were derivatized with the aim of improving the initial solubility, binding affinity, and target specificity. We used NMR to monitor solubility changes, binding affinity, and specific binding to the SL1 binding pocket during the fragment derivatization campaign. Compounds scoring the best in all three categories were further tested for their inhibitory effect on SL1 in a cell-free translation assay, where the best two compounds, A.2 and A.13, showed both significant and selective inhibition. Our results demonstrate that small molecules targeting translation initiation of SARS-CoV-2 can be rapidly obtained using NMR-guided medicinal chemistry, and that the correlation between affinity, selectivity, and in situ function of the derived compounds is still to be explored.

Abstract. In structured RNAs, helical elements are often capped by apical loops that are integral structural elements, ranging from 3 to >20 nts of size

The Vera C. Rubin Observatory will publish its first images on 23 June 2025 and will in future explore dark matter and dark energy as well as distant galaxies, supernovae and active centres of galaxie...

The three-dimensional (3D) atomistic-resolution structure and dynamics of RNA kissing complexes (KCs) and extended duplexes (EDs), homodimers formed through palindromic base pairing, are crucial for u...

Mas et al introduce in-cyclo NMR to quantify all states and kinetic steps of Hsp70 chaperones ATPase cycle. In-cyclo NMR will enable studies of other molecular machines at an unprecedented level of de...

NuFold: End-to-End Approach for RNA Tertiary Structure Prediction with Flexible Nucleobase Center Representation - kiharalab/NuFold

NMRFx is an integrated family of NMR processing programs

The vascular endothelial growth factor (VEGF) promoter region, which is involved in cancer progression, contains guanine-rich sequences capable of forming G-quadruplex (G4) structures. G4s play a crit...

NPSL2 is a stem loop element within the oncomiR-1 polycistronic primary microRNA (miRNA) cluster. NPSL2 is predicted to mediate conformational rearrangements within oncomiR-1 to regulate the biogenesi...