Evidence map›Paper›PMID 37024459›Full record

ArticleNature communications2023

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

Wenjuan Dong, Jing Wang, Lei Tian, Jianying Zhang, Erik W Settles, Chao Qin, Daniel R Steinken-Kollath, Ashley N Itogawa, Kimberly R Celona, Jinhee Yi and 14 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Observational
  3. Article
  4. Review
  5. Review
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 5 institutions in 1 country.

Wenjuan Dong *Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Jing Wang *Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Lei Tian *Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Jianying ZhangDepartment of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Erik W SettlesPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.ORCID 0000-0003-4331-3683
Chao QinSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Daniel R Steinken-KollathPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Ashley N ItogawaPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Kimberly R CelonaPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Jinhee YiPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Mitchell BryantPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Heather MeadPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Sierra A JaramilloPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
Hongjia LuDepartment of Molecular Microbiology and Immunology, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA.
Aimin LiPathology Core of Shared Resources Core, Beckman Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Ross E ZumwaltDepartment of Pathology, University of New Mexico, Albuquerque, NM, 87131, USA.
Sanjeet DadwalDivision of Infectious Diseases, Department of Medicine, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
Pinghui FengSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.ORCID 0000-0002-8494-0205
Weiming YuanDepartment of Molecular Microbiology and Immunology, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA.ORCID 0000-0002-4780-7157
Sean P J WhelanDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID 0000-0003-1564-8590
Paul S KeimPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.ORCID 0000-0003-0089-5820
Bridget Marie BarkerPathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.ORCID 0000-0002-3439-4517
Michael A CaligiuriDepartment of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. mcaligiuri@coh.org.ORCID 0000-0002-4095-3020
Jianhua YuDepartment of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. jiayu@coh.org.ORCID 0000-0002-0326-3223
Northern Arizona University · USCity Of Hope National Medical Center · USUniversity of Southern California · USUniversity of New Mexico · USWashington University in St. Louis · US

Funding

The Tumor Microenvironmental Barrier to Effective Viral OncolysisP01CA163205 · NCI · OHIO STATE UNIVERSITY · PI Xiaokui Mo · 2013 to 2026
$26.0M
Human natural killer cells: Advancing biology and clinical applicationsR35CA210087 · NCI · OHIO STATE UNIVERSITY · PI MICHAEL A CALIGIURI · 2017 to 2026
$8.3M
Explore roles of HSV-1 in Alzheimer's disease using mouse modelsR01AG070904 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEN, CASEY, FENG, PINGHUI · 2021 to 2025
$3.9M
Targeting FLT3 for the Treatment of Relapsed or Refractory Acute Myeloid LeukemiaR01CA265095 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI BUDDE, LIHUA ELIZABETH, CALIGIURI, MICHAEL A · 2021 to 2025
$2.4M
Characterizing and Targeting the Novel IL-15- AKT-XBP1s Pathway in NK CellsR01CA247550 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI YU, JIANHUA · 2020 to 2024
$2.2M
Elucidate and Modulate Cell Signaling in NK Cells for Glioma TreatmentR01AI129582 · NIAID · OHIO STATE UNIVERSITY · PI YU, JIANHUA · 2017 to 2021
$2.1M
NFAT activation in kGPCR tumorigenesisR01CA221521 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FENG, PINGHUI · 2017 to 2021
$1.9M
Overcoming Barriers of Virotherapy by Next-Generation oHSV Expressing E-CadherinR01NS106170 · NINDS · OHIO STATE UNIVERSITY · PI YU, JIANHUA · 2018 to 2023
$1.9M
Phase 1 Evaluation of Enhanced Natural Killer Cells as a Treatment Strategy in Non-Small cell Lung Cancer Patients Refractory to PD-1/PD-L1 Immune Checkpoint InhibitorsR01CA266457 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI VILLALONA, MIGUEL A, YU, JIANHUA · 2022 to 2025
$1.8M
NCI NIH HHS P01 CA163205NCI NIH HHS R01 CA221521NCI NIH HHS R01 CA247550NCI NIH HHS R01 CA265095NCI NIH HHS R01 CA266457NCI NIH HHS R35 CA210087NIAID NIH HHS R01 AI129582NIA NIH HHS R01 AG070904NINDS NIH HHS R01 NS106170
6 · The paper itself

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.

Indexed as

COVID-19Factor XaAntiviral AgentsHumansRivaroxabanSARS-CoV-2Spike Glycoprotein, CoronavirusVirus InternalizationAntiviral AgentsFactor XaRivaroxabanSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID37024459
PMCPMC10079155
OpenAlexW4362663410

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.