tetano
Editor, Senior Moderator
Pain
. 2020 Oct 1.
doi: 10.1097/j.pain.0000000000002097. Online ahead of print.
SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia
Aubin Moutal[SUP] 1 [/SUP], Laurent F Martin[SUP] 2 [/SUP], Lisa Boinon[SUP] 1 [/SUP], Kimberly Gomez[SUP] 1 [/SUP], Dongzhi Ran[SUP] 1 [/SUP], Yuan Zhou[SUP] 1 [/SUP], Harrison J Stratton[SUP] 1 [/SUP], Song Cai[SUP] 1 [/SUP], Shizhen Luo[SUP] 1 [/SUP], Kerry Beth Gonzalez[SUP] 1 [/SUP], Samantha Perez-Miller[SUP] 1 2 [/SUP], Amol Patwardhan[SUP] 1 2 3 [/SUP], Mohab M Ibrahim[SUP] 1 2 3 [/SUP], Rajesh Khanna[SUP] 1 2 4 3 [/SUP]
Affiliations
Abstract
Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2's Spike protein to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both Spike protein and vascular endothelial growth factor-A (VEGF-A) - a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuronal firing was blocked by Spike protein and NRP-1 inhibitor EG00229. Pro-nociceptive behaviors of VEGF-A were similarly blocked via 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 via subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.
. 2020 Oct 1.
doi: 10.1097/j.pain.0000000000002097. Online ahead of print.
SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia
Aubin Moutal[SUP] 1 [/SUP], Laurent F Martin[SUP] 2 [/SUP], Lisa Boinon[SUP] 1 [/SUP], Kimberly Gomez[SUP] 1 [/SUP], Dongzhi Ran[SUP] 1 [/SUP], Yuan Zhou[SUP] 1 [/SUP], Harrison J Stratton[SUP] 1 [/SUP], Song Cai[SUP] 1 [/SUP], Shizhen Luo[SUP] 1 [/SUP], Kerry Beth Gonzalez[SUP] 1 [/SUP], Samantha Perez-Miller[SUP] 1 2 [/SUP], Amol Patwardhan[SUP] 1 2 3 [/SUP], Mohab M Ibrahim[SUP] 1 2 3 [/SUP], Rajesh Khanna[SUP] 1 2 4 3 [/SUP]
Affiliations
- PMID: 33009246
- DOI: 10.1097/j.pain.0000000000002097
Abstract
Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2's Spike protein to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both Spike protein and vascular endothelial growth factor-A (VEGF-A) - a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuronal firing was blocked by Spike protein and NRP-1 inhibitor EG00229. Pro-nociceptive behaviors of VEGF-A were similarly blocked via 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 via subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.