Neuropilins: C-end rule peptides and their association with nociception and COVID-19

Graphical abstract Binding of the SARS-CoV-2 S1 CendR peptide to neuropilin-1 aids host invasion, while the binding of the VEGF-A 164 CendR peptide is associated with nociception.
Viral internalization is aided by host cell surface receptors. In the case of SARS-CoV-2 and SARS-CoV, the primary host receptor is the angiotensin-converting enzyme 2 (ACE2). Considering the disparities in the transmission rate and viral tropism of the two coronaviruses, additional host factors were suspected. Recently, a novel host factor for SARS-CoV-2 entry, neuropilin-1 (NRP-1) has been identified. These receptors potentiate viral infection in the presence of other host factors like ACE2. Through its C-end rule (CendR) motif exposed following furin processing, the SARS-CoV-2 spike protein binds to the CendR pocket of NRP-1 and achieves cell entry through endocytosis. The binding of SARS-CoV-2 spike protein to the NRP-1 receptor interferes with the docking of its endogenous ligand VEGF-A, signaling that would otherwise promote nociception. This review looks at the function of neuropilins and how it contributes to SARS-CoV-2 infection and nociception.