Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses

Letko, Michael; Marzi, Andrea; Munster, Vincent J.

doi:10.1038/s41564-020-0688-y

Cited by 2,860 publications

(3,195 citation statements)

References 38 publications

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“…To confirm these results, we evaluated entry into BHK cells and observed that transient transfection with hACE2 rendered them susceptible to transduction with SARS-CoV-2 S-MLV ( Figure 1B). These results demonstrate hACE2 is a functional receptor for SARS-CoV-2, in agreement with recently reported findings (Hoffmann et al, 2020;Letko et al, 2020;Zhou et al, 2020).…”

Section: Ace2 Is An Entry Receptor For Sars-cov-2supporting

confidence: 93%

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Walls

Park

Tortorici

et al. 2020

Cell

7,666

258

8,384

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Graphical AbstractHighlights d SARS-CoV-2 uses ACE2 to enter target cells d SARS-CoV-2 and SARS-CoV bind with similar affinities to ACE2 d Structures of SARS-CoV-2 spike glycoprotein in two conformations d SARS-CoV polyclonal antibodies inhibit SARS-CoV-2 spikemediated entry into cellsIn Brief SARS-CoV-2, a newly emerged pathogen spreading worldwide, binds with high affinity to human ACE2 and uses it as an entry receptor to invade target cells.Cryo-EM structures of the SARS-CoV-2 spike glycoprotein in two distinct conformations, along with inhibition of spike-mediated entry by SARS-CoV polyclonal antibodies, provide a blueprint for the design of vaccines and therapeutics. SUMMARYThe emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S 1 /S 2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

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Section: Ace2 Is An Entry Receptor For Sars-cov-2supporting

confidence: 93%

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Walls

Park

Tortorici

et al. 2020

Cell

7,666

258

8,384

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“…Human (30). Structural and functional analysis showed that the spike for SARS-CoV-2 also bound to ACE2 (31)(32)(33). ACE2 expression was high in lung, heart, ileum, kidney and bladder (34).…”

Section: Mechanism Of Sars-cov-2 Invasion Into Host Cellsmentioning

confidence: 99%

COVID-19 pathophysiology: A review

Yuki

Fujiogi

Koutsogiannaki

2020

Clinical Immunology

1,706

1,712

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“…It is supposed that the entry of the virus to human cells increases the inflammatory activity through various mechanisms with consequent release of pro-inflammatory cytokines, which cause serious damage, specially to the respiratory tract (12). Theoretically, it is assumed that a decrease in the activity of ACE2 in cell membranes may reduce the ability of SARS-CoV-2 to penetrate cells (13).…”

Section: Sars-cov-2: Prevalence Phylogenetics Taxonomy and Structurmentioning

confidence: 99%

Oleoylethanolamide, A Bioactive Lipid Amide, as A Promising Treatment Strategy for Coronavirus/COVID-19

Ghaffari

Roshanravan

Ostadrahimi

et al. 2020

Archives of Medical Research

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E20_423 2 (WHO) as a global pandemic. With the emergence of the COVID-19 virus and considering the lack of effective pharmaceutical treatment for it, there is an urgent need to identify safe and effective drugs or potential adjuvant therapy in this regard. Bioactive lipids with an array of known healthpromoting properties can be suggested as effective agents in alleviating acute respiratory stress induced by virus. The bioactive lipid amide, oleoylethanolamide (OEA), due to several distinctive homeostatic properties, including anti-inflammatory activities, modulation of immune response, and anti-oxidant effects can be considered as a novel potential pharmacological alternative for the management of COVID-19.

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Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses

Cited by 2,860 publications

References 38 publications

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

COVID-19 pathophysiology: A review

Oleoylethanolamide, A Bioactive Lipid Amide, as A Promising Treatment Strategy for Coronavirus/COVID-19

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