SARS-CoV-2 and MERS-CoV Spike Protein Binding Studies Support Stable Mimic of Bound 9-O-Acetylated Sialic Acids

被引:7
作者
Oh, Lisa [1 ]
Varki, Ajit [2 ,3 ]
Chen, Xi [1 ]
Wang, Lee-Ping [1 ]
机构
[1] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA
[2] Univ Calif San Diego, Glycobiol Res & Training Ctr, Dept Med, San Diego, CA 92093 USA
[3] Univ Calif San Diego, Glycobiol Res & Training Ctr, Dept Cellular & Mol Med, San Diego, CA 92093 USA
基金
美国国家卫生研究院;
关键词
SARS-CoV-2; MERS-CoV; CoV S protein; sialic acid; MM-PBSA; SOMD; binding free energy simulations; molecular dynamics; MOLECULAR-DYNAMICS SIMULATIONS; FREE-ENERGY; QUANTUM-CHEMISTRY; FORCE-FIELD; AMBER; CORONAVIRUS; PREDICTIONS; MECHANICS; SOLVENT; COMPLEX;
D O I
10.3390/molecules27165322
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Many disease-causing viruses target sialic acids (Sias), a class of nine-carbon sugars known to coat the surface of many cells, including those in the lungs. Human beta coronaviridae, known for causing respiratory tract diseases, often bind Sias, and some preferentially bind to those with 9-O-Ac-modification. Currently, co-binding of SARS-CoV-2, a beta coronavirus responsible for the COVID-19 pandemic, to human Sias has been reported and its preference towards alpha 2-3-linked Neu5Ac has been shown. Nevertheless, O-acetylated Sias-protein binding studies are difficult to perform, due to the ester lability. We studied the binding free energy differences between Neu5,9Ac2 alpha 2-3Gal beta pNP and its more stable 9-NAc mimic binding to SARS-CoV-2 spike protein using molecular dynamics and alchemical free energy simulations. We identified multiple Sia-binding pockets, including two novel sites, with similar binding affinities to those of MERS-CoV, a known co-binder of sialic acid. In our binding poses, 9-NAc and 9-OAc Sias bind similarly, suggesting an experimentally reasonable mimic to probe viral mechanisms.
引用
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页数:14
相关论文
共 70 条
[1]  
[Anonymous], OEDOCKING 331
[2]  
[Anonymous], Sire molecular simulation framework
[3]   The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoV [J].
Awasthi, Mayanka ;
Gulati, Sahil ;
Sarkar, Debi P. ;
Tiwari, Swasti ;
Kateriya, Suneel ;
Ranjan, Peeyush ;
Verma, Santosh Kumar .
VIRUSES-BASEL, 2020, 12 (09)
[4]   The SARS-COV-2 Spike Protein Binds Sialic Acids and Enables Rapid Detection in a Lateral Flow Point of Care Diagnostic Device [J].
Baker, Alexander N. ;
Richards, Sarah-Jane ;
Guy, Collette S. ;
Congdon, Thomas R. ;
Hasan, Muhammad ;
Zwetsloot, Alexander J. ;
Gallo, Angelo ;
Lewandowski, Jozef R. ;
Stansfeld, Phillip J. ;
Straube, Anne ;
Walker, Marc ;
Chessa, Simona ;
Pergolizzi, Giulia ;
Dedola, Simone ;
Field, Robert A. ;
Gibson, Matthew, I .
ACS CENTRAL SCIENCE, 2020, 6 (11) :2046-2052
[5]  
Brockhausen I., 2009, ESSENTIALS GLYCOBIOL, V2nd
[6]   MD-TASK: a software suite for analyzing molecular dynamics trajectories [J].
Brown, David K. ;
Penkler, David L. ;
Amamuddy, Olivier Sheik ;
Ross, Caroline ;
Atilgan, Ali Rana ;
Atilgan, Canan ;
Bishop, Ozlem Tastan .
BIOINFORMATICS, 2017, 33 (17) :2768-2771
[7]  
Case D. A., 2020, AMBER 20
[8]  
Cheeseman J.R., 2016, Gaussian 16
[9]  
Clausen TM, 2020, CELL, V183, P1043, DOI [10.1016/j.cell.2020.09.033, 10.1101/2020.07.14.201616]
[10]   ACE2: Evidence of role as entry receptor for SARS-CoV-2 and implications in comorbidities [J].
Cuervo, Natalia Zamorano ;
Grandvaux, Nathalie .
ELIFE, 2020, 9