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.

Highlights d A screen in Drosophila identifies glial molecules with vital functions for neurons d Depletion of glial ferritin heavy chain results in iron-mediated axonal damage d Ferritin heavy chain is secreted by oligodendrocytes in mice

Silicon and boron share many similarities, both chemically and biochemically, including having similar effects on bone, although their mechanisms of action are not known. Here we compared the loading of silicon and boron into bone, their localization and how they are influenced by age (growth & development), to obtain further clues as to the biological effects of these elements and, especially, to see if they behave the same or not. Bone samples were obtained from two different studies where female Sprague Dawley rats had been maintained on a normal maintenance diet for up to 43 weeks. Total bone elemental levels were determined by ICP-OES following microwave assisted acid digestion. Silicon and boron levels in the decalcified bones (i.e. the collagen fraction) were also investigated. Silicon and boron showed marked differences in loading and in their localization in bone. Highest silicon and lowest boron concentrations were found in the under-mineralized bone of younger rats and lowest silicon and highest boron concentrations were found in the fully mineralized bone of the adult rat. Overall, however total bone silicon content increased with age, as did boron content, the latter mirroring the increase in calcium (mineral) content of bone. However, whereas silicon showed equal distribution in the collagen and mineral fractions of bone, boron was exclusively localized in the mineral fraction. These findings confirm the reported association between silicon and collagen, especially at the early stages of bone mineralization, and show that boron is associated with the bone mineral but not connective tissues. These data suggest that silicon and boron have different biological roles and that one is unlikely, therefore, to substitute for the other, or at least boron would not substitute for Si in the connective tissues. Finally, we noted that silicon levels in the mineral fraction varied greatly between the two studies, suggesting that one or more nutritional factor(s) may influence the loading of Si into the mineral fraction of bone. This and the nature of the interaction between Si and collagen deserve further attention.

Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague–Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n = 8–10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2–6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague–Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than previously estimated which could explain why absolute silicon deficiency is difficult to achieve but, when it is achieved in young growing animals, it results in stunted growth and abnormal development of bone and other connective tissues.