可溶性CD4通过靶向内体受体结合位点抑制埃博拉病毒感染

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-05-02 DOI:10.1016/j.isci.2025.112573

Leah Liu Wang , Patrick Keiser , Derek Yang , Javier Seravalli , J.J. Patten , Brett Eaton , Dirk Anderson , Yi Liu , Michael R. Holbrook , Amos B. Smith III , Robert A. Davey , Shi-Hua Xiang

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引用次数: 0

摘要

众所周知，人类CD4（分化簇4）是人类免疫缺陷病毒（HIV）进入细胞的主要受体。病毒与CD4分子结合，诱导病毒糖蛋白（GP） gp120的构象变化，从而暴露出协受体CCR5或CXCR4的共受体结合位点。然后，共受体结合导致病毒进入的膜融合。由于CD4分子对gp120具有高亲和力，可溶性CD4 （sCD4）和CD4模拟小分子（CD4mcs）作为HIV感染的潜在抑制剂被广泛研究。令人惊讶的是，我们发现人类sCD4和一些CD4mcs能够抑制埃博拉病毒（EBOV）感染。有证据表明，这些化合物通过靶向内体受体尼曼-匹克C1 （NPC1）的GP结合位点来阻断病毒进入。这一发现揭示了两种远程病毒（HIV和EBOV）之间病毒受体结合的相似性，并为EBOV进入抑制剂提供了新的可能性。

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Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding site

Human CD4 (cluster of differentiation 4) is well known as the primary receptor for human immunodeficiency virus (HIV) entry into the cells. The virus binds to CD4 molecules to induce a conformational change in the viral glycoprotein (GP) gp120, which exposes the co-receptor binding site for coreceptors CCR5 or CXCR4. The co-receptor binding then leads to membrane fusion for viral entry. Since the CD4 molecule has a high affinity for gp120, soluble CD4 (sCD4) and CD4-mimetic small molecules (CD4mcs) have been extensively studied as potential inhibitors for HIV infection. Surprisingly, we have found that human sCD4 and some CD4mcs are able to inhibit Ebola virus (EBOV) infection. Evidence is provided that the compounds block viral entry by targeting the GP binding site for the endosomal receptor Niemann-Pick C1 (NPC1). This finding reveals virus-receptor binding similarities between two remote viruses (HIV and EBOV) and suggests new possibilities for EBOV entry inhibitors.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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