Neuropilin‑1 as a new potential SARS‑CoV‑2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID‑19

Abstract

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the cause of the new viral infectious disease (coronavirus disease 2019; COVID-19). Emerging evidence indicates that COVID-19 may be associated with a wide spectrum of neurological symptoms and complications with central nervous system (CNS) involvement. It is now well-established that entry of SARS-CoV-2 into host cells is facilitated by its spike proteins mainly through binding to the angiotensin-converting enzyme 2 (ACE-2). Preclinical studies have suggested that neuropilin-1 (NRP1), which is a transmembrane receptor that lacks a cytosolic protein kinase domain and exhibits high expression in the respiratory and olfactory epithelium, may also be implicated in COVID-19 by enhancing the entry of SARS-CoV-2 into the brain through the olfactory epithelium. In the present study, we expand on these findings and demonstrate that the NRP1 is also expressed in the CNS, including olfactory-related regions such as the olfactory tubercles and paraolfactory gyri. This furthers supports the potential role of NRP1 as an additional SARS-CoV-2 infection mediator implicated in the neurologic manifestations of COVID-19. Accordingly, the neurotropism of SARS-CoV-2 via NRP1-expressing cells in the CNS merits further investigation.