PT  - JOURNAL ARTICLE
AU  - Moutal, Aubin
AU  - Martin, Laurent F.
AU  - Boinon, Lisa
AU  - Gomez, Kimberly
AU  - Ran, Dongzhi
AU  - Zhou, Yuan
AU  - Stratton, Harrison J.
AU  - Cai, Song
AU  - Luo, Shizhen
AU  - Gonzalez, Kerry Beth
AU  - Perez-Miller, Samantha
AU  - Patwardhan, Amol
AU  - Ibrahim, Mohab M.
AU  - Khanna, Rajesh
TI  - SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia
AID  - 10.1101/2020.07.17.209288
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.17.209288
4099  - http://biorxiv.org/content/early/2020/09/14/2020.07.17.209288.short
4100  - http://biorxiv.org/content/early/2020/09/14/2020.07.17.209288.full
AB  - 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.Competing Interest StatementR. Khanna is the co-founder of Regulonix LLC, a company developing non-opioids drugs for chronic pain. In addition, R. Khanna has patents US10287334 and US10441586 issued to Regulonix LLC. The other authors declare no competing financial interests.ACE2Angiotensin converting enzyme 2AUCarea under the curveCaV2.2N-type voltage-gated calcium channelCOVID-19coronavirus disease 2019DRGdorsal root gangliaMEAmulti-well microelectrode arrayNaV1.7voltage-gated sodium channel isoform 7NRP-1Neuropilin-1PWTspaw withdrawal thresholdsSARS-CoV-2Severe acute respiratory syndrome coronavirus 2sEPSCsspontaneous excitatory postsynaptic currentsSNIspared nerve injuryVEGF-Avascular endothelial growth factor-A