Related Experiment Video
Updated: Oct 8, 2025

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit
Published on: June 28, 2013
Understanding COVID-19 Pathogenesis: A Drug-Repurposing Effort to Disrupt Nsp-1 Binding to Export Machinery Receptor
Sona Vasudevan1, James N Baraniuk2
1Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057, USA.
Abstract:
Non-structural protein 1 (Nsp1) is a virulence factor found in all beta coronaviruses (b-CoVs). Recent studies have shown that Nsp1 of SARS-CoV-2 virus interacts with the nuclear export receptor complex, which includes nuclear RNA export factor 1 (NXF1) and nuclear transport factor 2-like export factor 1 (NXT1). The NXF1-NXT1 complex plays a crucial role in the transport of host messenger RNA (mRNA). Nsp1 interferes with the proper binding of NXF1 to mRNA export adaptors and its docking to the nuclear pore complex. We propose that drugs targeting the binding surface between Nsp1 and NXF1-NXT1 may be a useful strategy to restore host antiviral gene expression. Exploring this strategy forms the main goals of this paper. Crystal structures of Nsp1 and the heterodimer of NXF1-NXT1 have been determined. We modeled the docking of Nsp1 to the NXF1-NXT1 complex, and discovered repurposed drugs that may interfere with this binding. To our knowledge, this is the first attempt at drug-repurposing of this complex. We used structural analysis to screen 1993 FDA-approved drugs for docking to the NXF1-NXT1 complex. The top hit was ganirelix, with a docking score of -14.49. Ganirelix competitively antagonizes the gonadotropin releasing hormone receptor (GNRHR) on pituitary gonadotrophs, and induces rapid, reversible suppression of gonadotropin secretion. The conformations of Nsp1 and GNRHR make it unlikely that they interact with each other. Additional drug leads were inferred from the structural analysis of this complex, which are discussed in the paper. These drugs offer several options for therapeutically blocking Nsp1 binding to NFX1-NXT1, which may normalize nuclear export in COVID-19 infection.
Related Concept Videos
Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Leaky Scanning
Principles of Drug Action
Drugs can be agonists or antagonists. Like the endogenous ligands, agonists always bind and activate the target to produce a cellular response. Agonist binding induces a conformational change which in turn...
Nuclear Export
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
Regulation of Nuclear Protein Sorting
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...

