Coronaviruses Use ACE2 Monomers as Entry‐Receptors

Eiring, Patrick; Klein, Teresa; Backes, Simone; Streit, Marcel; Doose, Sören; Beliu, Gerti; Sauer, Markus; Jungblut, Marvin

doi:10.1002/anie.202300821

Cited by 8 publications

(7 citation statements)

References 47 publications

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“…This could explain why certain cell lines with a weak ACE2 expression level are prone to infection caused by SARS-CoV-2. 23,56,57 Sialylated gangliosides or glycans can aid in the attachment of the virus to these cell lines. Also, our results highlight that antiviral molecules or composites targeting the virus−ganglioside interaction can effectively block the membrane/cellular attachment of SARS-CoV-2 and thereby inhibit the cellular infection caused by the virus.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Hence, we conclude that together GD1a and ACE2 molecules result in a synergistic binding of SARS-CoV-2 on SMBs, which in turn increases the binding kinetics (R ON data) and surface coverage of bound virus particles. This could explain why certain cell lines with a weak ACE2 expression level are prone to infection caused by SARS-CoV-2. ,, Sialylated gangliosides or glycans can aid in the attachment of the virus to these cell lines. Also, our results highlight that antiviral molecules or composites targeting the virus–ganglioside interaction can effectively block the membrane/cellular attachment of SARS-CoV-2 and thereby inhibit the cellular infection caused by the virus.…”

Section: Discussionmentioning

confidence: 99%

“…22 This led to the speculation that the viral infection cannot be directly correlated to the ACE2 expression level and that other cellular attachment factors are required for the efficient infection of the lower lungs. Recently Eiring et al 23 reported that endogenous ACE2 within host cells predominantly exists in its monomeric state and this monomeric ACE2 interacts with the S protein of SARS-CoV-2, and the cellular infection efficiency exhibits significant variation across distinct cell lines that possess comparable ACE2 expression levels. The authors indicated that glycosphingolipids, including gangliosides, may engage in interactions with the membrane receptors of host cells, facilitating the process of viral entry.…”

Section: ■ Introductionmentioning

confidence: 99%

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Synergistic Binding of SARS-CoV-2 to ACE2 and Gangliosides in Native Lipid Membranes

Dey,

Sharma,

Dhanawat

et al. 2024

ACS Infect. Dis.

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Viruses utilize cell surface glycans and plasma membrane receptors to attain an adequate attachment strength for initiating cellular entry. We show that SARS-CoV-2 particles bind to endogenous ACE2 receptors and added sialylated gangliosides in near-native membranes. This was explored using supported membrane bilayers (SMBs) that were formed using plasma membrane vesicles having endogenous ACE2 and GD1a gangliosides reconstituted in lipid vesicles. The virus binding rate to the SMBs is influenced by GD1a and inhibition of the ganglioside reduces the extent of virus binding to the membrane receptors. Using combinations of inhibition assays, we confirm that added GD1a in lipid membranes increases the availability of the endogenous ACE2 receptor and results in the synergistic binding of SARS-CoV-2 to the membrane receptors in SMBs.

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Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Synergistic Binding of SARS-CoV-2 to ACE2 and Gangliosides in Native Lipid Membranes

Dey,

Sharma,

Dhanawat

et al. 2024

ACS Infect. Dis.

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“…A recent study by Eiring et al reports that endogenous ACE2 in host cells exists in the monomeric form and interacts with the S protein of SARS-CoV-2. [27] Thereby, exogenous expression of the proteins may not well represent the native condition for the virus or S protein binding.…”

Section: Introductionmentioning

confidence: 99%

Giant Plasma Membrane Vesicles as Cellular‐Mimics for Probing SARS‐CoV‐2 Binding at Single Particle Level

Dey,

Dhanawat,

Gupta

et al. 2023

ChemistrySelect

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Membrane receptors, attachment factors and various other membrane factors play a critical role in the specific attachment of virus particles to a cell surface. Researchers have been employing a range of model systems starting from receptor‐reconstituted lipid membranes to live cells for quantitative evaluation of virus‐receptor/attachment factor interactions. In this work, we show that giant plasma membrane vesicles (GPMVs) derived from adherent cells are a suitable cell‐mimicking model system to examine the binding of SARS‐CoV‐2 to cellular receptors. We evaluated the binding of cell‐cultured SARS‐CoV‐2 to GPMVs by imaging single virus particles with the wide‐field fluorescence microscopy technique. The GPMVs were derived from three different cell lines, i. e., Vero, HEK293T and A549. We compared the number of bound virus particles per cell, cell‐attached GPMV, and cell‐free GPMV of three different cell lines. We explain the observed trend in the data from the expression level of endogenous ACE2 protein and also, conclude that the protein is functional in GPMVs for virus and antibody binding.

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“…Among all viral components, surface binding proteins are a key factor in viral infections. The specificity of these proteins is decisive for host cell binding and can vary considerably; in the case of SARS-CoV-2 infection, the binding of its spike protein to cellular ACE2 receptors is crucial, whereas other virus species use surface proteins with a comparatively broad tropism, such as the G protein of VSV (Figure a). − …”

mentioning

confidence: 99%

Re-Engineered Pseudoviruses for Precise and Robust 3D Mapping of Viral Infection

Jungblut,

Backes,

Streit

et al. 2023

ACS Nano

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Engineered vesicular stomatitis virus (VSV) pseudotyping offers an essential method for exploring virus−cell interactions, particularly for viruses that require high biosafety levels. Although this approach has been employed effectively, the current methodologies for virus visualization and labeling can interfere with infectivity and lead to misinterpretation of results. In this study, we introduce an innovative approach combining genetic code expansion (GCE) and click chemistry with pseudotyped VSV to produce highly fluorescent and infectious pseudoviruses (clickVSVs). These clickVSVs enable robust and precise virus−cell interaction studies without compromising the biological function of the viral surface proteins. We evaluated this approach by generating VSVs bearing a unique chemical handle for click labeling and assessing the infectivity in relevant cell lines. Our results demonstrate that clickVSVs maintain their infectivity post-labeling and present an efficiency about two times higher in detecting surface proteins compared to classical immunolabeling. The utilization of clickVSVs further allowed us to visualize and track 3D virus binding and infection in living cells, offering enhanced observation of virus−host interactions. Thus, clickVSVs provide an efficient alternative for virus-associated research under the standard biosafety levels.

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Coronaviruses Use ACE2 Monomers as Entry‐Receptors

Cited by 8 publications

References 47 publications

Synergistic Binding of SARS-CoV-2 to ACE2 and Gangliosides in Native Lipid Membranes

Synergistic Binding of SARS-CoV-2 to ACE2 and Gangliosides in Native Lipid Membranes

Giant Plasma Membrane Vesicles as Cellular‐Mimics for Probing SARS‐CoV‐2 Binding at Single Particle Level

Re-Engineered Pseudoviruses for Precise and Robust 3D Mapping of Viral Infection

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