Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein

By J. Millet, Gary R. Whittaker. Proceedings of the National Academy of Sciences of the United States of America, 2014

684 citations recorded by the source corpus.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/0c214aa940d78ad45cf2742d9d1e92701c62d66a

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Citations in the corpus

Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion (2020, neutral): “…S cleavage by host proteases at the boundary between the S1 and S2 subunits (S1/S2), in a subset of coronaviruses, and at a conserved site upstream of the fusion peptide (S2’) in all known coronaviruses (Belouzard et al., 2009; Burkard et al., 2014; Millet and Whittaker, 2014; Park et al., 2016).”
Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus (2015, background): “The S1/S2 boundary in MERS-CoV spike (defined as the region between the RBD and the fusion peptide) contains one established human protease motif that is recognized by proprotein convertases (hPPC) (15, 16); it also contains one established human protease motif that is recognized by endosomal cystei”
The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade (2020, background): “This furin-like cleavage site, is supposed to be cleaved during virus egress (Mille and Whittaker, 2014) for S-protein “priming” and may provide a gain-of-function to the 2019-nCoV for efficient spreading in the human population compared to other lineage b betacoronaviruses.”
Structural insights into coronavirus entry (2019, background): “Liu, 2009) and/or substitutions of residues at the S1/S2 or S2’ cleavage sites (Belouzard et al., 2009; Li et al., 2015; Millet and Whittaker, 2014; Wicht et al., 2014; Yang et al., 2015).”
TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells (2020, background): “However, it is still controversial whether MERS-CoV is activated by furin in human airway epithelial cells (38, 39, 40, 41).”
Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak (2020, neutral): “We found that the SARS-CoV-2 S protein contains a putative furin recognition motif (PRRARSV) (Figure 4) similar to that of MERS-CoV, which has a PRSVRSVmotif that is likely cleaved by furin [16, 17] during virus egress.”
Molecular immune pathogenesis and diagnosis of COVID-19 (2020, neutral): “two-step furin activation for membrane fusion[21].”
Human Coronavirus: Host-Pathogen Interaction. (2019, background): “Interestingly, whereas the S1/S2 site was cleaved during the synthesis of MERS-CoV S protein, the other site (S2′) was cleaved during viral entry (84).”
SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract (2020, neutral): “See also Figure S2. ll Article 2020; Millet and Whittaker, 2014; Wicht et al., 2014).”
A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells (2020, neutral): “Thus, the Middle East respiratory syndrome coronavirus spike protein (MERS-S) is activated by a two-step process: MERS-S is first cleaved by furin at the S1/S2 site in infected cells, which is required for subsequent TMPRSS2-mediated cleavage at the S20 site (Figure 1A) during viral entry into lung ”
Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry (2019, background): “1A, 1B), resulting in a weakened spike structure and allowing the S2’ 200 site to become exposed to proteases (51).”
Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen (2017, background): “and can be mediated by several proteases, including furin, TMPRSS2, and cathepsin L (11, 13, 38).”
Glycan Shield and Fusion Activation of a Deltacoronavirus Spike Glycoprotein Fine-Tuned for Enteric Infections (2017, background): “For a subset of coronaviruses, such as mouse hepatitis coronavirus (MHV), SARS-CoV, and MERS-CoV, the S glycoprotein is cleaved at the S1/S2 junction during biogenesis and viral egress (10–13).”