Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding site
Summary: 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...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422500834X |
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| author | 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 |
| author_facet | 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 |
| author_sort | Leah Liu Wang |
| collection | DOAJ |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-2edd30f45b4940a9af2eb660fba2f19f |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-2edd30f45b4940a9af2eb660fba2f19f2025-08-20T03:47:41ZengElsevieriScience2589-00422025-06-0128611257310.1016/j.isci.2025.112573Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding siteLeah Liu Wang0Patrick Keiser1Derek Yang2Javier Seravalli3J.J. Patten4Brett Eaton5Dirk Anderson6Yi Liu7Michael R. Holbrook8Amos B. Smith, III9Robert A. Davey10Shi-Hua Xiang11School of Veterinary Medicine and Biomedical Sciences and Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USANational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 0211, USADepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Biochemistry and Nebraska Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE 68588, USANational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 0211, USAIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, Frederick, MD 21702, USADepartment of Biochemistry and Nebraska Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE 68588, USAHolland Computing Center, University of Nebraska-Lincoln, Lincoln, NE 68588, USAIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, Frederick, MD 21702, USADepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USANational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 0211, USASchool of Veterinary Medicine and Biomedical Sciences and Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S258900422500834XBiological sciencesImmunologyMicrobiologyNatural sciencesVirology |
| spellingShingle | 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 Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding site iScience Biological sciences Immunology Microbiology Natural sciences Virology |
| title | Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding site |
| title_full | Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding site |
| title_fullStr | Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding site |
| title_full_unstemmed | Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding site |
| title_short | Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding site |
| title_sort | soluble cd4 inhibits ebola virus infection by targeting endosomal receptor binding site |
| topic | Biological sciences Immunology Microbiology Natural sciences Virology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422500834X |
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