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This structural snapshot describes the structural bases underlying the pandemic capacity of SARS\u2010CoV\u20102 and explains its fast motion over respiratory epithelia that allow its rapid cellular entry. Based on notable viral spike (S) protein features, we propose that the flat sialic acid\u2010binding domain at the N\u2010terminal domain (NTD) of the S1 subunit leads to more effective first contact and interaction with the sialic acid layer over the epithelium, and this, in turn, allows faster viral \u2018surfing\u2019 of the epithelium and receptor scanning by SARS\u2010CoV\u20102. Angiotensin\u2010converting enzyme 2 (ACE\u20102) protein on the epithelial surface is the primary entry receptor for SARS\u2010CoV\u20102, and protein\u2013protein interaction assays demonstrate high\u2010affinity binding of the spike protein (S protein) to ACE\u20102. To date, no high\u2010frequency mutations were detected at the C\u2010terminal domain of the S1 subunit in the S protein, where the receptor\u2010binding domain (RBD) is located. Tight binding to ACE\u20102 by a conserved viral RBD suggests the ACE2\u2010RBD interaction is likely optimal. Moreover, the viral S subunit contains a cleavage site for furin and other proteases, which accelerates cell entry by SARS\u2010CoV\u20102. The model proposed here describes a structural basis for the accelerated host cell entry by SARS\u2010CoV\u20102 relative to other HCoVs and also discusses emerging hypotheses that are likely to contribute to the development of antiviral strategies to combat the pandemic capacity of SARS\u2010CoV\u20102.<\/jats:p>","DOI":"10.1111\/febs.15651","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T17:37:40Z","timestamp":1606930660000},"page":"5010-5020","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":138,"title":["The structural basis of accelerated host cell entry by SARS\u2010CoV\u20102\u2020"],"prefix":"10.1111","volume":"288","author":[{"given":"Murat","family":"Seyran","sequence":"first","affiliation":[{"name":"Doctoral Studies in Natural and Technical Sciences (SPL 44) University of Vienna Austria"},{"name":"Infection, Malignancy and Autoimmunity (NIIMA) Universal Scientific Education and Research Network (USERN) Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Takayama","sequence":"additional","affiliation":[{"name":"Center for iPS Cell Research and Application Kyoto University Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir N.","family":"Uversky","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Morsani College of Medicine University of South Florida Tampa FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Lundstrom","sequence":"additional","affiliation":[{"name":"PanTherapeutics Lutry Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Pal\u00f9","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samendra P.","family":"Sherchan","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Tulane University New Orleans LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diksha","family":"Attrish","sequence":"additional","affiliation":[{"name":"Dr. B R Ambedkar Center for Biomedical Research (ACBR) University of Delhi (North Camps) Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nima","family":"Rezaei","sequence":"additional","affiliation":[{"name":"Research Center for Immunodeficiencies Pediatrics Center of Excellence, Children's Medical Center Tehran University of Medical Sciences Iran"},{"name":"Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA) Universal Scientific Education and Research Network (USERN) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa A. 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