Your company account is blocked and you cannot place orders. If you have questions, please contact your company administrator.

Discovery of Small Molecules Targeting the Frameshifting Element RNA in SARS-CoV-2 Viral Genome.

Basic Information

ID: ALA5247673

Journal: ACS Med Chem Lett

Title: Discovery of Small Molecules Targeting the Frameshifting Element RNA in SARS-CoV-2 Viral Genome.

Authors: Yang M, Olatunji FP, Rhodes C, Balaratnam S, Dunne-Dombrink K, Seshadri S, Liang X, Jones CP, Le Grice SFJ, Ferré-D'Amaré AR, Schneekloth JS.

Abstract: Targeting structured RNA elements in the SARS-CoV-2 viral genome with small molecules is an attractive strategy for pharmacological control over viral replication. In this work, we report the discovery of small molecules that target the frameshifting element (FSE) in the SARS-CoV-2 RNA genome using high-throughput small-molecule microarray (SMM) screening. A new class of aminoquinazoline ligands for the SARS-CoV-2 FSE are synthesized and characterized using multiple orthogonal biophysical assays and structure-activity relationship (SAR) studies. This work reveals compounds with mid-micromolar binding affinity (KD = 60 ± 6 μM) to the FSE RNA and supports a binding mode distinct from previously reported FSE binders MTDB and merafloxacin. In addition, compounds are active in in vitro dual-luciferase and in-cell dual-fluorescent-reporter frameshifting assays, highlighting the promise of targeting structured elements of RNAs with druglike compounds to alter expression of viral proteins.

CiteXplore: 37312842

DOI: 10.1021/acsmedchemlett.3c00051

Patent ID: