Another host factor for SARS-CoV-2 Virus-host interactions determine cellular entry and spreading in tissues. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the earlier SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as a receptor; however, their tissue tropism differs, raising the possibility that additional host factors are involved. The spike protein of SARS-CoV-2 contains a cleavage site for the protease furin that is absent from SARS-CoV (see the Perspective by Kielian). Cantuti-Castelvetri et al. now show that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial and epithelial cells. Daly et al. found that the furin-cleaved S1 fragment of the spike protein binds directly to cell surface NRP1 and blocking this interaction with a small-molecule inhibitor or monoclonal antibodies reduced viral infection in cell culture. Understanding the role of NRP1 in SARS-CoV-2 infection may suggest potential targets for future antiviral therapeutics. Science, this issue p. 856, p. 861; see also p. 765 NRP1 serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19. The causative agent of coronavirus 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. In this study, 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 olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.

中文翻译：

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Neuropilin-1 促进 SARS-CoV-2 细胞进入和感染

SARS-CoV-2 病毒-宿主相互作用的另一个宿主因素决定了细胞进入和在组织中的扩散。严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）和早期的SARS-CoV使用血管紧张素转换酶2（ACE2）作为受体；然而，它们的组织趋向性不同，这增加了涉及其他宿主因素的可能性。SARS-CoV-2 的刺突蛋白包含 SARS-CoV 中不存在的蛋白酶弗林蛋白酶切割位点（参见 Kielian 的观点）。Cantuti-Castelvetri 等。现在表明，已知可结合弗林蛋白酶裂解底物的神经纤毛蛋白 1 (NRP1) 可增强 SARS-CoV-2 的感染性。NRP1 在呼吸和嗅觉上皮细胞中大量表达，在内皮细胞和上皮细胞中表达最高。戴利等人。发现刺突蛋白的弗林蛋白酶切割的 S1 片段直接与细胞表面 NRP1 结合并阻断这种与小分子抑制剂或单克隆抗体的相互作用，从而减少了细胞培养中的病毒感染。了解 NRP1 在 SARS-CoV-2 感染中的作用可能为未来抗病毒治疗提供潜在的靶点。科学，这个问题 p。856 页。861; 另见第 765 NRP1 作为 SARS-CoV-2 感染的宿主因子，可能为 COVID-19 提供治疗靶点。2019 年冠状病毒病 (COVID-19) 的病原体是严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2)。对于许多病毒，组织嗜性是由病毒受体和宿主细胞表面的进入辅因子的可用性决定的。在这项研究中，我们发现neuropilin-1 (NRP1)，已知结合弗林蛋白酶裂解的底物，显着增强 SARS-CoV-2 感染性，这种作用被针对 NRP1 的单克隆阻断抗体阻断。具有改变的弗林蛋白酶裂解位点的 SARS-CoV-2 突变体不依赖于 NRP1 的传染性。从人类 COVID-19 尸检中获得的嗅觉上皮的病理分析表明，SARS-CoV-2 感染了面向鼻腔的 NRP1 阳性细胞。我们的数据提供了对 SARS-CoV-2 细胞感染性的洞察，并确定了抗病毒干预的潜在目标。从人类 COVID-19 尸检中获得的嗅觉上皮的病理分析表明，SARS-CoV-2 感染了面向鼻腔的 NRP1 阳性细胞。我们的数据提供了对 SARS-CoV-2 细胞感染性的洞察，并确定了抗病毒干预的潜在目标。从人类 COVID-19 尸检中获得的嗅觉上皮的病理分析表明，SARS-CoV-2 感染了面向鼻腔的 NRP1 阳性细胞。我们的数据提供了对 SARS-CoV-2 细胞感染性的洞察，并确定了抗病毒干预的潜在目标。