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The ACE2 receptor a...
The ACE2 receptor accelerates but is not biochemically required for SARS-CoV-2 membrane fusion
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- Cervantes, Marcos (author)
- Univ Virginia, Dept Mol Physiol & Biomed Engn, Charlottesville, VA 22908 USA
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- Hess, Tobin (author)
- Univ Virginia, Dept Mol Physiol & Biomed Engn, Charlottesville, VA 22908 USA
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- Morbioli, Giorgio G. G. (author)
- Univ Virginia, Dept Mol Physiol & Biomed Engn, Charlottesville, VA 22908 USA.;Tufts Univ, Dept Chem, Lab Living Devices, Medford, MA 02155 USA
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- Sengar, Anjali (author)
- Univ Virginia, Dept Mol Physiol & Biomed Engn, Charlottesville, VA 22908 USA
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- Kasson, Peter M. (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär biofysik,Univ Virginia, Dept Mol Physiol & Biomed Engn, Charlottesville, VA 22908 USA
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Univ Virginia, Dept Mol Physiol & Biomed Engn, Charlottesville, VA 22908 USA Univ Virginia, Dept Mol Physiol & Biomed Engn, Charlottesville, VA 22908 USA;Tufts Univ, Dept Chem, Lab Living Devices, Medford, MA 02155 USA (creator_code:org_t)
- Royal Society of Chemistry, 2023
- 2023
- English.
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In: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 14:25, s. 6997-7004
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Abstract
Subject headings
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- The SARS-CoV-2 coronavirus infects human cells via the ACE2 receptor. Structural evidence suggests that ACE2 may not just serve as an attachment factor but also conformationally activate the SARS-CoV-2 spike protein for membrane fusion. Here, we test that hypothesis directly, using DNA-lipid tethering as a synthetic attachment factor in place of ACE2. We find that SARS-CoV-2 pseudovirus and virus-like particles are capable of membrane fusion without ACE2 if activated with an appropriate protease. Thus, ACE2 is not biochemically required for SARS-CoV-2 membrane fusion. However, addition of soluble ACE2 speeds up the fusion reaction. On a per-spike level, ACE2 appears to promote activation for fusion and then subsequent inactivation if an appropriate protease is not present. Kinetic analysis suggests at least two rate-limiting steps for SARS-CoV-2 membrane fusion, one of which is ACE2 dependent and one of which is not. Since ACE2 serves as a high-affinity attachment factor on human cells, the possibility to replace it with other factors implies a flatter fitness landscape for host adaptation by SARS-CoV-2 and future related coronaviruses.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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