Neuropilin 1 facilitates SARS CoV 2 cell entry and provides a possible pathway into the central nervous system
The causative agent of the current pandemic and coronavirus disease 2019 (COVID 19) is the severe acute respiratory syndrome coronavirus 2 (SARS CoV 2)1. Understanding how SARS CoV 2 enters and spreads within human organs is crucial for developing strategies to prevent viral dissemination. For many viruses, tissue tropism is determined by the availability of virus receptors on the surface of host cells2. Both SARS CoV and SARS CoV 2 use angiotensin converting enzyme 2 (ACE2) as a host receptor, yet, their tropisms differ3 5. Here, we found that the cellular receptor neuropilin 1 (NRP1) known to bind furin cleaved substrates, significantly potentiates SARS CoV 2 infectivity, which was inhibited by a monoclonal blocking antibody against the extracellular b1b2 domain of NRP1. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial cells and in the epithelial cells facing the nasal cavity. Neuropathological analysis of human COVID 19 autopsies revealed SARS CoV 2 infected NRP1 positive cells in the olfactory epithelium and bulb. In the olfactory bulb infection was detected particularly within NRP1 positive endothelial cells of small capillaries and medium sized vessels. Studies in mice demonstrated, after intranasal application, NRP1 mediated transport of virus sized particles into the central nervous system. Thus, NRP1 could explain the enhanced tropism and spreading of SARS CoV 2.