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. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), uses the viral spike (S) protein for host cell attachment and entry. The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. Cleavage of S generates a polybasic Arg-Arg-Ala-Arg carboxyl-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface neuropilin-1 (NRP1) and NRP2 receptors. We used x-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction by RNA interference or selective inhibitors reduced SARS-CoV-2 entry and infectivity in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19.

中文翻译：

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Neuropilin-1 是 SARS-CoV-2 感染的宿主因子

SARS-CoV-2 病毒与宿主相互作用的另一个宿主因素决定了细胞进入和组织中的传播。严重急性呼吸综合征冠状病毒 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，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的切割位点（参见 Kielian 的 Perspective）。Cantuti-Castelvetri 等人。现在表明，已知可结合弗林蛋白酶切割底物的神经纤维蛋白 1 (NRP1) 可增强 SARS-CoV-2 的感染性。NRP1 在呼吸和嗅觉上皮中大量表达，在内皮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，并阻止这种与小分子抑制剂或单克隆抗体的相互作用减少了细胞培养物中的病毒感染。了解 NRP1 在 SARS-CoV-2 感染中的作用可能会为未来的抗病毒治疗提供潜在的靶点。科学，本期第 3 页。第 856 页，第 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。严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是 2019 年冠状病毒病 (COVID-19) 的病原体，它使用病毒刺突 (S) 蛋白来附着和进入宿主细胞。宿主蛋白酶弗林蛋白酶将全长前体 S 糖蛋白切割成两个相关的多肽：S1 和 S2。S 的切割在 S1 上生成了一个多碱基 Arg-Arg-Ala-Arg 羧基末端序列，该序列符合与细胞表面神经纤维蛋白 1 (NRP1) 和 NRP2 受体结合的 C 端规则 (CendR) 基序。我们使用 X 射线晶体学和生化方法来表明 S1 CendR 基序直接结合 NRP1。通过 RNA 干扰或选择性抑制剂阻断这种相互作用会降低 SARS-CoV-2 在细胞培养中的进入和感染性。因此，NRP1 可作为 SARS-CoV-2 感染的宿主因子，并可能为 COVID-19 提供治疗靶点。通过 RNA 干扰或选择性抑制剂阻断这种相互作用会降低 SARS-CoV-2 在细胞培养中的进入和感染性。因此，NRP1 可作为 SARS-CoV-2 感染的宿主因子，并可能为 COVID-19 提供治疗靶点。通过 RNA 干扰或选择性抑制剂阻断这种相互作用会降低 SARS-CoV-2 在细胞培养中的进入和感染性。因此，NRP1 可作为 SARS-CoV-2 感染的宿主因子，并可能为 COVID-19 提供治疗靶点。