Author: So Young Kim; Weihua Jin; Amika Sood; David W. Montgomery; Oliver C. Grant; Mark M. Fuster; Li Fu; Jonathan S. Dordick; Robert J. Woods; Fuming Zhang; Robert J. Linhardt
Title: Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry Document date: 2020_4_15
ID: fs8dn7ir_1
Snippet: In March 2020, the World Health Organization declared severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) a pandemic less than three months after its initial emergence in Wuhan, China [1, 2] . SARS-CoV-2 is a zoonotic Betacoronavirus transmitted through person-person contact through airborne and fecal-oral routes, and has caused over 693,000 confirmed coronavirus disease 2019 (COVID-19) cases and 33,000 associated deaths worldwid.....
Document: In March 2020, the World Health Organization declared severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) a pandemic less than three months after its initial emergence in Wuhan, China [1, 2] . SARS-CoV-2 is a zoonotic Betacoronavirus transmitted through person-person contact through airborne and fecal-oral routes, and has caused over 693,000 confirmed coronavirus disease 2019 (COVID-19) cases and 33,000 associated deaths worldwide [2] [3] [4] [5] . While there is limited understanding of SARS-CoV-2 pathogenesis, extensive studies have been performed on how its closely related cousins, SARS-CoV and MERS-CoV (Middle East respiratory syndrome-related coronavirus), invade host cell. Upon initially contacting the surface of a host cell, SARS-CoV and MERS-CoV exploit host cell proteases to prime their surface spike glycoproteins (SGPs) for fusion activation, which is achieved by receptor binding, low pH, or both [6, 7] . The receptor binding domain (RBD) resides within subunit 1 (S1) while subunit 2 (S2) facilitates viral-host cell membrane fusion [6] . Activated SGP undergoes a conformational change followed by an initiated fusion reaction with the host cell membrane [6] . Endocytosed virions are further processed by the endosomal protease cathepsin L in the late endosome [7, 8] . Both MERS-Cov and SARS-CoV require proteolytic cleavage at their S2' site, but not at their S1-S2 junction, for successful membrane fusion and host cell entry [6, 7] . Additionally, receptors involved in fusion activation of SARS-CoV and MERS-CoV include heparan sulfate (HS) and angiotensinconverting enzyme 2 (ACE2), and dipeptidyl peptidase 4 (DPP4), respectively [9] [10] [11] .
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