Betrixaban is a broad anti-virus inhibitor by activating innate immunity
The innate immune system serves as the first line of defense against viral infections. Type I interferon (IFN-I) signaling, in particular, plays a crucial role in mediating antiviral immunity. Here, we identify Betrixaban (BT), a novel small-molecule compound that activates innate immune responses,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1603530/full |
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| author | Shiyu Hu Yang Zhao Xingyu Chen Haocheng Wang Wenjun Hu Rong Huang Jian Yang Chenxi Niu Xuefei Guo Fuping You |
| author_facet | Shiyu Hu Yang Zhao Xingyu Chen Haocheng Wang Wenjun Hu Rong Huang Jian Yang Chenxi Niu Xuefei Guo Fuping You |
| author_sort | Shiyu Hu |
| collection | DOAJ |
| description | The innate immune system serves as the first line of defense against viral infections. Type I interferon (IFN-I) signaling, in particular, plays a crucial role in mediating antiviral immunity. Here, we identify Betrixaban (BT), a novel small-molecule compound that activates innate immune responses, leading to broad-spectrum antiviral effects. BT induces IFN-β production and upregulates interferon-stimulated genes (ISGs), effectively suppressing the replication of multiple viruses, including vesicular stomatitis virus (VSV), herpes simplex virus type 1 (HSV-1), murine hepatitis virus strain A59 (MHV-A59), encephalomyocarditis virus (EMCV), and influenza A virus (IAV). BT’s antiviral activity relies on innate immune activation, with IRF3 playing a key role. The antiviral effect was significantly reduced upon loss of ISGs induction, including Mx1 and Mx2. In vivo, BT treatment markedly induced IFNB1 expression across multiple mouse tissues and significantly inhibited viral replication in VSV-infected wild-type mice, confirming the essential role of innate antiviral immune activation. These findings establish BT as a potent stimulator of the innate immune system, demonstrating broad-spectrum antiviral potential and highlighting its promise as a therapeutic agent. |
| format | Article |
| id | doaj-art-6412a19c47b44a279871cf583e0c340f |
| institution | Kabale University |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-6412a19c47b44a279871cf583e0c340f2025-08-21T05:27:23ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-08-011510.3389/fcimb.2025.16035301603530Betrixaban is a broad anti-virus inhibitor by activating innate immunityShiyu Hu0Yang Zhao1Xingyu Chen2Haocheng Wang3Wenjun Hu4Rong Huang5Jian Yang6Chenxi Niu7Xuefei Guo8Fuping You9Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, National Health Commission (NHC) Key Laboratory of Medical Immunology, Peking University Health Science Center, Beijing, ChinaInstitute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, National Health Commission (NHC) Key Laboratory of Medical Immunology, Peking University Health Science Center, Beijing, ChinaInstitute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, National Health Commission (NHC) Key Laboratory of Medical Immunology, Peking University Health Science Center, Beijing, ChinaInstitute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, National Health Commission (NHC) Key Laboratory of Medical Immunology, Peking University Health Science Center, Beijing, ChinaDepartment of Orthopedics and Traumatology, Nanchong Hospital of Traditional Chinese Medicine, Nanchong, ChinaInstitute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, ChinaInstitute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, ChinaDepartment of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, ChinaInstitute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, National Health Commission (NHC) Key Laboratory of Medical Immunology, Peking University Health Science Center, Beijing, ChinaInstitute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, National Health Commission (NHC) Key Laboratory of Medical Immunology, Peking University Health Science Center, Beijing, ChinaThe innate immune system serves as the first line of defense against viral infections. Type I interferon (IFN-I) signaling, in particular, plays a crucial role in mediating antiviral immunity. Here, we identify Betrixaban (BT), a novel small-molecule compound that activates innate immune responses, leading to broad-spectrum antiviral effects. BT induces IFN-β production and upregulates interferon-stimulated genes (ISGs), effectively suppressing the replication of multiple viruses, including vesicular stomatitis virus (VSV), herpes simplex virus type 1 (HSV-1), murine hepatitis virus strain A59 (MHV-A59), encephalomyocarditis virus (EMCV), and influenza A virus (IAV). BT’s antiviral activity relies on innate immune activation, with IRF3 playing a key role. The antiviral effect was significantly reduced upon loss of ISGs induction, including Mx1 and Mx2. In vivo, BT treatment markedly induced IFNB1 expression across multiple mouse tissues and significantly inhibited viral replication in VSV-infected wild-type mice, confirming the essential role of innate antiviral immune activation. These findings establish BT as a potent stimulator of the innate immune system, demonstrating broad-spectrum antiviral potential and highlighting its promise as a therapeutic agent.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1603530/fullbroad-spectrum antiviralBetrixabanFXainnate immunityVSV |
| spellingShingle | Shiyu Hu Yang Zhao Xingyu Chen Haocheng Wang Wenjun Hu Rong Huang Jian Yang Chenxi Niu Xuefei Guo Fuping You Betrixaban is a broad anti-virus inhibitor by activating innate immunity Frontiers in Cellular and Infection Microbiology broad-spectrum antiviral Betrixaban FXa innate immunity VSV |
| title | Betrixaban is a broad anti-virus inhibitor by activating innate immunity |
| title_full | Betrixaban is a broad anti-virus inhibitor by activating innate immunity |
| title_fullStr | Betrixaban is a broad anti-virus inhibitor by activating innate immunity |
| title_full_unstemmed | Betrixaban is a broad anti-virus inhibitor by activating innate immunity |
| title_short | Betrixaban is a broad anti-virus inhibitor by activating innate immunity |
| title_sort | betrixaban is a broad anti virus inhibitor by activating innate immunity |
| topic | broad-spectrum antiviral Betrixaban FXa innate immunity VSV |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1603530/full |
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