ESCPE-1 mediates retrograde endosomal sorting of the SARS-CoV-2 host factor Neuropilin-1

Proc Natl Acad Sci U S A. 2022 Jun 21;119(25):e2201980119. doi: 10.1073/pnas.2201980119. Epub 2022 Jun 13.


Endosomal sorting maintains cellular homeostasis by recycling transmembrane proteins and associated proteins and lipids (termed "cargoes") from the endosomal network to multiple subcellular destinations, including retrograde traffic to the trans-Golgi network (TGN). Viral and bacterial pathogens subvert retrograde trafficking machinery to facilitate infectivity. Here, we develop a proteomic screen to identify retrograde cargo proteins of the endosomal SNX-BAR sorting complex promoting exit 1 (ESCPE-1). Using this methodology, we identify Neuropilin-1 (NRP1), a recently characterized host factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as a cargo directly bound and trafficked by ESCPE-1. ESCPE-1 mediates retrograde trafficking of engineered nanoparticles functionalized with the NRP1-interacting peptide of the SARS-CoV-2 spike (S) protein. CRISPR-Cas9 deletion of ESCPE-1 subunits reduces SARS-CoV-2 infection levels in cell culture. ESCPE-1 sorting of NRP1 may therefore play a role in the intracellular membrane trafficking of NRP1-interacting viruses such as SARS-CoV-2.

Keywords: COVID-19; Neuropilin-1; SARS-CoV-2; endosome; sorting nexin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / metabolism
  • COVID-19* / virology
  • CRISPR-Cas Systems
  • Endosomes* / virology
  • Gene Deletion
  • Host-Pathogen Interactions*
  • Humans
  • Nanoparticles
  • Neuropilin-1* / genetics
  • Neuropilin-1* / metabolism
  • Proteomics
  • SARS-CoV-2* / metabolism
  • Sorting Nexins / metabolism
  • Spike Glycoprotein, Coronavirus / metabolism


  • NRP1 protein, human
  • Sorting Nexins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Neuropilin-1