The causative agent of coronavirus induced disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. Here, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of human COVID-19 autopsies revealed SARS-CoV-2 infected cells including olfactory neuronal cells facing the nasal cavity positive for NRP1. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.

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 cells 2 . Both SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as a host receptor, yet, their tropisms differ 3-5 . 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.

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Tick-borne encephalitis virus (TBEV) is a growing health concern. It causes a severe disease that can lead to permanent neurological complications or death and the incidence of TBEV infections is constantly rising. Our understanding of TBEV’s structure lags behind that of other flaviviruses, but has advanced recently with the publication of a high-resolution structure of the TBEV virion. The gaps in our knowledge include: aspects of receptor binding, replication and virus assembly. Furthermore, TBEV has mostly been studied in mammalian systems, even though the virus’ interaction with its tick hosts is a central part of its life cycle. Elucidating these aspects of TBEV biology are crucial for the development of TBEV antivirals, as well as the improvement of diagnostics. In this review, we summarise the current structural knowledge on TBEV, bringing attention to the current gaps in our understanding, and propose further research that is needed to truly understand the structural-functional relationship of the virus and its hosts.