Phosphatidylserine Receptors Enhance SARS-CoV-2 Infection: AXL as a Therapeutic Target for COVID-19

Dana Bohan; Hanora Van Ert; Natalie Ruggio; Kai J Rogers; Mohammad Badreddine; José A Aguilar-Briseño; Roberth Anthony Rojas Chavez; Boning Gao; Tomasz Stokowy; Eleni Christakou; David Micklem; Gro Gausdal; Hillel Haim; John Minna; James B Lorens; Wendy Maury

doi:10.1101/2021.06.15.448419

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Phosphatidylserine Receptors Enhance SARS-CoV-2 Infection: AXL as a Therapeutic Target for COVID-19

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Phosphatidylserine Receptors Enhance SARS-CoV-2 Infection: AXL as a Therapeutic Target for COVID-19

Dana Bohan, Hanora Van Ert, Natalie Ruggio, Kai J Rogers, Mohammad Badreddine, José A Aguilar-Briseño, Roberth Anthony Rojas Chavez, Boning Gao, Tomasz Stokowy, Eleni Christakou, …

bioRxiv : the preprint server for biology

06/24/2021

DOI: 10.1101/2021.06.15.448419

PMCID: PMC8219095

PMID: 34159331

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https://doi.org/10.1101/2021.06.15.448419View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Phosphatidylserine (PS) receptors are PS binding proteins that mediate uptake of apoptotic bodies. Many enveloped viruses utilize this PS/PS receptor mechanism to adhere to and internalize into the endosomal compartment of cells and this is termed apoptotic mimicry. For viruses that have a mechanism(s) of endosomal escape, apoptotic mimicry is a productive route of virus entry. We evaluated if PS receptors serve as cell surface receptors for SARS-CoV-2 and found that the PS receptors, AXL, TIM-1 and TIM-4, facilitated virus infection when low concentrations of the SARS-CoV-2 cognate receptor, ACE2, was present. Consistent with the established mechanism of PS receptor utilization by other viruses, PS liposomes competed with SARS-CoV-2 for binding and entry. We demonstrated that this PS receptor enhances SARS-CoV-2 binding to and infection of an array of human lung cell lines and is an under-appreciated but potentially important host factor facilitating SARS-CoV-2 entry.

ACE2

SARS-CoV-2

COVID19

apoptotic mimicry

AXL

viral entry

TMPRSS2

bemcentinib

phosphatidylserine receptor

TIM-1

Details

Title: Subtitle: Phosphatidylserine Receptors Enhance SARS-CoV-2 Infection: AXL as a Therapeutic Target for COVID-19
Creators: Dana Bohan - University of Iowa
Hanora Van Ert - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA
Natalie Ruggio - University of Iowa
Kai J Rogers - University of Iowa
Mohammad Badreddine - University of Iowa
José A Aguilar-Briseño - University of Iowa
Roberth Anthony Rojas Chavez - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA
Boning Gao - The University of Texas Southwestern Medical Center
Tomasz Stokowy - University of Bergen
Eleni Christakou - University of Bergen
David Micklem - BerGenBio (Norway)
Gro Gausdal - BerGenBio (Norway)
Hillel Haim - University of Iowa
John Minna - The University of Texas Southwestern Medical Center
James B Lorens - University of Bergen
Wendy Maury - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv : the preprint server for biology
DOI: 10.1101/2021.06.15.448419
PMID: 34159331
PMCID: PMC8219095
Grant note: T32 AI007511 / NIAID NIH HHS P50 CA070907 / NCI NIH HHS U54 CA260560 / NCI NIH HHS T32 GM007337 / NIGMS NIH HHS R01 AI134733 / NIAID NIH HHS
Language: English
Date posted: 06/24/2021
Academic Unit: Microbiology and Immunology
Record Identifier: 9984297629702771

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