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

Title: SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia
Authors: Moutal, Aubin; Martin, Laurent F.; Boinon, Lisa; Gomez, Kimberly; Ran, Dongzhi; Zhou, Yuan; Stratton, Harrison J.; Cai, Song; Luo, Shizhen; Gonzalez, Kerry Beth; Perez-Miller, Samantha; Patwardhan, Amol; Ibrahim, Mohab M.; Khanna, Rajesh
Source: Pain ; volume 162, issue 1, page 243-252 ; ISSN 0304-3959 1872-6623
Publisher Information: Ovid Technologies (Wolters Kluwer Health)
Publication Year: 2020
Description: 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.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1097/j.pain.0000000000002097
Availability: https://doi.org/10.1097/j.pain.0000000000002097; https://journals.lww.com/10.1097/j.pain.0000000000002097
Rights: http://creativecommons.org/licenses/by-nc-nd/4.0/
Accession Number: edsbas.BC58B4A3
Database: BASE