SARS-CoV-2, Early Entry Events
Viruses are obligate intracellular parasites, and host cell entry is the first step in the viral life cycle. The SARS-CoV-2 (COVID-19) entry process into susceptible host tissue cells is complex requiring (1) attachment of the virus via the conserved spike (S) protein receptor-binding motif (RBM) to...
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doaj-c9c0477682004b8287cd9402f022f10d2020-12-07T09:08:28ZengHindawi LimitedJournal of Pathogens2090-30572090-30652020-01-01202010.1155/2020/92386969238696SARS-CoV-2, Early Entry EventsJames P. Chambers0Jieh Yu1James J. Valdes2Bernard P. Arulanandam3South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USASouth Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USASouth Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USASouth Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USAViruses are obligate intracellular parasites, and host cell entry is the first step in the viral life cycle. The SARS-CoV-2 (COVID-19) entry process into susceptible host tissue cells is complex requiring (1) attachment of the virus via the conserved spike (S) protein receptor-binding motif (RBM) to the host cell angiotensin-converting-enzyme 2 (ACE2) receptor, (2) S protein proteolytic processing, and (3) membrane fusion. Spike protein processing occurs at two cleavage sites, i.e., S1/S2 and S2′. Cleavage at the S1/S2 and S2′ sites ultimately gives rise to generation of competent fusion elements important in the merging of the host cell and viral membranes. Following cleavage, shedding of the S1 crown results in significant conformational changes and fusion peptide repositioning for target membrane insertion and fusion. Identification of specific protease involvement has been difficult due to the many cell types used and studied. However, it appears that S protein proteolytic cleavage is dependent on (1) furin and (2) serine protease transmembrane protease serine 2 proteases acting in tandem. Although at present not clear, increased SARS-CoV-2 S receptor-binding motif binding affinity and replication efficiency may in part account for observed differences in infectivity. Cleavage of the ACE2 receptor appears to be yet another layer of complexity in addition to forfeiture and/or alteration of ACE2 function which plays an important role in cardiovascular and immune function.http://dx.doi.org/10.1155/2020/9238696 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
James P. Chambers Jieh Yu James J. Valdes Bernard P. Arulanandam |
spellingShingle |
James P. Chambers Jieh Yu James J. Valdes Bernard P. Arulanandam SARS-CoV-2, Early Entry Events Journal of Pathogens |
author_facet |
James P. Chambers Jieh Yu James J. Valdes Bernard P. Arulanandam |
author_sort |
James P. Chambers |
title |
SARS-CoV-2, Early Entry Events |
title_short |
SARS-CoV-2, Early Entry Events |
title_full |
SARS-CoV-2, Early Entry Events |
title_fullStr |
SARS-CoV-2, Early Entry Events |
title_full_unstemmed |
SARS-CoV-2, Early Entry Events |
title_sort |
sars-cov-2, early entry events |
publisher |
Hindawi Limited |
series |
Journal of Pathogens |
issn |
2090-3057 2090-3065 |
publishDate |
2020-01-01 |
description |
Viruses are obligate intracellular parasites, and host cell entry is the first step in the viral life cycle. The SARS-CoV-2 (COVID-19) entry process into susceptible host tissue cells is complex requiring (1) attachment of the virus via the conserved spike (S) protein receptor-binding motif (RBM) to the host cell angiotensin-converting-enzyme 2 (ACE2) receptor, (2) S protein proteolytic processing, and (3) membrane fusion. Spike protein processing occurs at two cleavage sites, i.e., S1/S2 and S2′. Cleavage at the S1/S2 and S2′ sites ultimately gives rise to generation of competent fusion elements important in the merging of the host cell and viral membranes. Following cleavage, shedding of the S1 crown results in significant conformational changes and fusion peptide repositioning for target membrane insertion and fusion. Identification of specific protease involvement has been difficult due to the many cell types used and studied. However, it appears that S protein proteolytic cleavage is dependent on (1) furin and (2) serine protease transmembrane protease serine 2 proteases acting in tandem. Although at present not clear, increased SARS-CoV-2 S receptor-binding motif binding affinity and replication efficiency may in part account for observed differences in infectivity. Cleavage of the ACE2 receptor appears to be yet another layer of complexity in addition to forfeiture and/or alteration of ACE2 function which plays an important role in cardiovascular and immune function. |
url |
http://dx.doi.org/10.1155/2020/9238696 |
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