Drug-Repurposing Screening Identifies a Gallic Acid Binding Site on SARS-CoV-2 Non-structural Protein 7

• DOI: 10.1021/acsptsci.2c00225
• Publication Date: 2023-03-07T14:46:16Z
• Authors: Yushu Gu; Miaomiao Liu; Bart L. Staker; Garry W. Buchko; Ronald J. Quinn
• Keywords: Drug repositioning; Docking (animal); Repurposing; Drug Development

SARS-CoV-2 is the agent responsible for acute respiratory disease COVID-19 and global pandemic initiated in early 2020. While record-breaking development of vaccines has assisted control COVID-19, there still a pressing demand antiviral drugs to halt destructive impact this disease. Repurposing clinically approved provides an opportunity expediate treatments into clinic. In effort facilitate drug repurposing, FDA-approved library containing 2400 compounds was screened against non-structural protein 7 (nsp7) using native mass spectrometry-based assay. Nsp7 one components replication/transcription complex essential optimal viral replication, perhaps serving off-load RNA from nsp8. From library, gallic acid identified as compound that bound tightly nsp7, with estimated Kd 15 μM. NMR chemical shift perturbation experiments were used map ligand-binding surface on indicating pocket centered protein's four α-helices (α2). The identification acid-binding site nsp7 may allow therapeutic via artificial-intelligence-based virtual docking other strategies.