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Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection.
Dong, Wenjuan; Wang, Jing; Tian, Lei; Zhang, Jianying; Settles, Erik W; Qin, Chao; Steinken-Kollath, Daniel R; Itogawa, Ashley N; Celona, Kimberly R; Yi, Jinhee; Bryant, Mitchell; Mead, Heather; Jaramillo, Sierra A; Lu, Hongjia; Li, Aimin; Zumwalt, Ross E; Dadwal, Sanjeet; Feng, Pinghui; Yuan, Weiming; Whelan, Sean P J; Keim, Paul S; Barker, Bridget Marie; Caligiuri, Michael A; Yu, Jianhua.
Afiliação
  • Dong W; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
  • Wang J; 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.
  • Zhang J; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
  • Settles EW; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
  • Qin C; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
  • Steinken-Kollath DR; Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
  • Itogawa AN; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
  • Celona KR; Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA.
  • Yi J; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, 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; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
  • Li A; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
  • Zumwalt RE; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
  • Dadwal S; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
  • Feng P; Department of Molecular Microbiology and Immunology, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA.
  • Yuan W; Pathology Core of Shared Resources Core, Beckman Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
  • Whelan SPJ; Department of Pathology, University of New Mexico, Albuquerque, NM, 87131, USA.
  • Keim PS; Division of Infectious Diseases, Department of Medicine, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
  • Barker BM; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
  • Caligiuri MA; Department of Molecular Microbiology and Immunology, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA.
  • Yu J; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Nat Commun ; 14(1): 1936, 2023 04 06.
Article em En | MEDLINE | ID: mdl-37024459
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator Xa / COVID-19 Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator Xa / COVID-19 Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos