Recombinant Human Neuropilin-1 Protein, CF

Neuropilin-1 protein (Nrp1, previously neuropilin; also CD304) is a 130 - 140 kDa type I transmembrane (TM) glycoprotein that regulates axon guidance and angiogenesis (1 - 4). The full-length 923 amino acid (aa) human NRP1 contains a 623 aa extracellular domain (ECD) that shows 92 - 95% aa identity with mouse, rat, bovine and canine NRP1 (3, 4). The NRP1 ECD contains two N-terminal CUB domains (termed a1a2), two domains with homology to coagulation factors V and VIII (b1b2) and a MAM (meprin) domain (c). C-terminally divergent splice variants with 704, 644, 609, and 551 aa lack the MAM and TM domains and are demonstrated or presumed to be soluble antagonists (1, 5 - 7). A 906 aa form lacks a TM segment, but secretion has not been found (8). The sema domains of Class III secreted semaphorins such as Sema3A bind NRP1 a1a2 (9). Heparin, the heparin-binding forms of VEGF (VEGF165, VEGF-B and VEGF-E), PlGF (PlGF2), and the C-terminus of Sema3 bind the b1b2 region (9, 10). NRP1 and NRP2 share 48% aa identity within the ECD and can form homo- and hetero-oligomers via interaction of their MAM domains (1). Neuropilins show partially overlapping expression in neuronal and endothelial cells during development (1, 2). Both neuropilins act as co-receptors with plexins, mainly plexin A3 and A4, to bind class III semaphorins that mediate axon repulsion (11). However, only NRP1 binds Sema3A, and only NRP2 binds Sema3F (1). Both are co-receptors with VEGF R2 (also called KDR or Flk-1) for VEGF165 binding (1). Sema3A signaling can be blocked by VEGF165, which has higher affinity for NRP1 (12). NRP1 is preferentially expressed in arteries during development or those undergoing remodeling (1, 2). NRP1 is also expressed on dendritic cells and mediates DC-induced T cell proliferation (13).

Neuropilin-1 has been shown to bind to the S1 domain of the SARS-CoV-2 Spike protein via its b1 domain (14,15). Blocking this interaction reduced viral entry and infectivity in vitro providing a new potential therapeutic target to treat COVID-19.