دورية أكاديمية
أعرض في EDS

Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection.

التفاصيل البيبلوغرافية
العنوان: Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection.
المؤلفون: Dong W; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Wang J; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Tian L; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Zhang J; Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Settles EW; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.; Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA., Qin C; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA., Steinken-Kollath DR; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Itogawa AN; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Celona KR; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Yi J; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Bryant M; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Mead H; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Jaramillo SA; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Lu H; Department of Molecular Microbiology and Immunology, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA., Li A; Pathology Core of Shared Resources Core, Beckman Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Zumwalt RE; Department of Pathology, University of New Mexico, Albuquerque, NM, 87131, USA., Dadwal S; Division of Infectious Diseases, Department of Medicine, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Feng P; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA., Yuan W; Department of Molecular Microbiology and Immunology, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA., Whelan SPJ; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA., Keim PS; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.; Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA., Barker BM; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.; Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA., Caligiuri MA; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. mcaligiuri@coh.org.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. mcaligiuri@coh.org.; City of Hope Comprehensive Cancer Center, Los Angeles, CA, 91010, USA. mcaligiuri@coh.org., Yu J; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. jiayu@coh.org.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. jiayu@coh.org.; City of Hope Comprehensive Cancer Center, Los Angeles, CA, 91010, USA. jiayu@coh.org.; Department of Immuno-Oncology, City of Hope, Los Angeles, CA, 91010, USA. jiayu@coh.org.
المصدر: Nature communications [Nat Commun] 2023 Apr 06; Vol. 14 (1), pp. 1936. Date of Electronic Publication: 2023 Apr 06.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, P.H.S.; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Factor Xa* , COVID-19*, Humans ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Rivaroxaban/pharmacology ; Rivaroxaban/therapeutic use ; SARS-CoV-2/metabolism ; Virus Internalization ; Antiviral Agents/pharmacology
مستخلص: Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation common in all pandemic variants. The anticoagulant rivaroxaban, a direct FXa inhibitor, inhibits FXa-mediated S protein cleavage and facilitates viral entry, whereas the indirect FXa inhibitor fondaparinux does not. In the lethal SARS-CoV-2 K18-hACE2 model, FXa prolongs survival yet its combination with rivaroxaban but not fondaparinux abrogates that protection. These results identify both a previously unknown function for FXa and an associated antiviral host defense mechanism against SARS-CoV-2 and suggest caution in considering direct FXa inhibitors for preventing or treating thrombotic complications in COVID-19 patients.
(© 2023. The Author(s).)
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معلومات مُعتمدة: R01 AI129582 United States AI NIAID NIH HHS; R01 CA266457 United States CA NCI NIH HHS; R35 CA210087 United States CA NCI NIH HHS; P01 CA163205 United States CA NCI NIH HHS; R01 CA247550 United States CA NCI NIH HHS; R01 CA221521 United States CA NCI NIH HHS; R01 NS106170 United States NS NINDS NIH HHS; R01 CA265095 United States CA NCI NIH HHS; R01 AG070904 United States AG NIA NIH HHS
المشرفين على المادة: EC 3.4.21.6 (Factor Xa)
0 (spike protein, SARS-CoV-2)
0 (Spike Glycoprotein, Coronavirus)
9NDF7JZ4M3 (Rivaroxaban)
0 (Antiviral Agents)
تواريخ الأحداث: Date Created: 20230406 Date Completed: 20230410 Latest Revision: 20240515
رمز التحديث: 20240515
مُعرف محوري في PubMed: PMC10079155
DOI: 10.1038/s41467-023-37336-9
PMID: 37024459
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-37336-9