It Takes Two to Tango: Secondary Entry Pathway for SARS-CoV-2 Induces Analgesia

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to impact the world, its mechanisms of action begin to unravel. The main entry pathway for SARS-CoV-2 into the cell is thought to be through binding to the angiotensin converting enzyme 2, but it seems another protein can induce its viral entry: neuropilin-1 receptor (NRP-1). NRP-1 is usually bound by vascular endothelial growth factor-A (VEGF-A), a - amongst other- pronociceptive factor. By binding to NRP-1, the Spike protein of SARS-CoV-2 blocks neuronal signaling, reducing the pro-nociceptive implication of VEGF-A. This analgesic role of SARS-CoV-2 gave rise to an increase in screenings for new compounds that could interfere with this pathway. Preventing VEGFA from binding to NRP1 opens new possibilities for therapeutic strategies in the field of neuropathic pain.