SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia

Pain. 2021 Jan;162(1):243-252. doi: 10.1097/j.pain.0000000000002097.

Abstract

Global spread of severe acute respiratory syndrome coronavirus 2 continues unabated. Binding of severe acute respiratory syndrome coronavirus 2's spike protein to host angiotensin-converting enzyme 2 triggers viral entry, but other proteins may participate, including the neuropilin-1 receptor (NRP-1). Because both spike protein and vascular endothelial growth factor-A (VEGF-A)-a pronociceptive and angiogenic factor, bind NRP-1, we tested whether spike could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuron firing was blocked by spike protein and NRP-1 inhibitor EG00229. Pronociceptive behaviors of VEGF-A were similarly blocked through suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A "silencing" of pain through subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / physiology
  • Humans
  • Neuropilin-1 / metabolism
  • Pain Measurement
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / pathogenicity*
  • Signal Transduction
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Spike Glycoprotein, Coronavirus
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • spike protein, SARS-CoV-2
  • Neuropilin-1