Open AccessSARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia
Author(s) -
Aubin Moutal,
Laurent Martin,
Lisa Boi,
Kimberly Gómez,
Dongzhi Ran,
Yuan Zhou,
Harrison J. Stratton,
Sanjun Cai,
Shizhen Luo,
Kerry Beth Gonzalez,
Samantha PerezMiller,
Amol Patwardhan,
Mohab Ibrahim,
Rajesh Khanna
Publication year - 2020
Publication title -
pain
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.524
H-Index - 258
eISSN - 1872-6623
pISSN - 0304-3959
DOI - 10.1097/j.pain.0000000000002097
Subject(s) - neuropilin 1 , receptor , vascular endothelial growth factor , medicine , microbiology and biotechnology , neuroscience , chemistry , biology , vegf receptors
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.