The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoV
COVID-19 novel coronavirus (CoV) disease caused by severe acquired respiratory syndrome (SARS)-CoV-2 manifests severe lethal respiratory illness in humans and has recently developed into a worldwide pandemic. The lack of effective treatment strategy and vaccines against the SARS-CoV-2 poses a threat...
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doaj-481dfddeafee4d148d5accad4bfb08792020-11-25T03:49:55ZengMDPI AGViruses1999-49152020-08-011290990910.3390/v12090909The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoVMayanka Awasthi0Sahil Gulati1Debi P. Sarkar2Swasti Tiwari3Suneel Kateriya4Peeyush Ranjan5Santosh Kumar Verma6Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USAGatan Inc., Pleasanton, CA 94588, USADepartment of Biochemistry, University of Delhi South Campus, New Delhi 110021, IndiaDepartment of Molecular Medicine & Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, IndiaSchool of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, IndiaDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USADepartment of Molecular Medicine & Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, IndiaCOVID-19 novel coronavirus (CoV) disease caused by severe acquired respiratory syndrome (SARS)-CoV-2 manifests severe lethal respiratory illness in humans and has recently developed into a worldwide pandemic. The lack of effective treatment strategy and vaccines against the SARS-CoV-2 poses a threat to human health. An extremely high infection rate and multi-organ secondary infection within a short period of time makes this virus more deadly and challenging for therapeutic interventions. Despite high sequence similarity and utilization of common host-cell receptor, human angiotensin-converting enzyme-2 (ACE2) for virus entry, SARS-CoV-2 is much more infectious than SARS-CoV. Structure-based sequence comparison of the N-terminal domain (NTD) of the spike protein of Middle East respiratory syndrome (MERS)-CoV, SARS-CoV, and SARS-CoV-2 illustrate three divergent loop regions in SARS-CoV-2, which is reminiscent of MERS-CoV sialoside binding pockets. Comparative binding analysis with host sialosides revealed conformational flexibility of SARS-CoV-2 divergent loop regions to accommodate diverse glycan-rich sialosides. These key differences with SARS-CoV and similarity with MERS-CoV suggest an evolutionary adaptation of SARS-CoV-2 spike glycoprotein reciprocal interaction with host surface sialosides to infect host cells with wide tissue tropism.https://www.mdpi.com/1999-4915/12/9/909SARS-CoV-2N-terminal domainspike glycoproteinMERS-CoV |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mayanka Awasthi Sahil Gulati Debi P. Sarkar Swasti Tiwari Suneel Kateriya Peeyush Ranjan Santosh Kumar Verma |
spellingShingle |
Mayanka Awasthi Sahil Gulati Debi P. Sarkar Swasti Tiwari Suneel Kateriya Peeyush Ranjan Santosh Kumar Verma The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoV Viruses SARS-CoV-2 N-terminal domain spike glycoprotein MERS-CoV |
author_facet |
Mayanka Awasthi Sahil Gulati Debi P. Sarkar Swasti Tiwari Suneel Kateriya Peeyush Ranjan Santosh Kumar Verma |
author_sort |
Mayanka Awasthi |
title |
The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoV |
title_short |
The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoV |
title_full |
The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoV |
title_fullStr |
The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoV |
title_full_unstemmed |
The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoV |
title_sort |
sialoside-binding pocket of sars-cov-2 spike glycoprotein structurally resembles mers-cov |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2020-08-01 |
description |
COVID-19 novel coronavirus (CoV) disease caused by severe acquired respiratory syndrome (SARS)-CoV-2 manifests severe lethal respiratory illness in humans and has recently developed into a worldwide pandemic. The lack of effective treatment strategy and vaccines against the SARS-CoV-2 poses a threat to human health. An extremely high infection rate and multi-organ secondary infection within a short period of time makes this virus more deadly and challenging for therapeutic interventions. Despite high sequence similarity and utilization of common host-cell receptor, human angiotensin-converting enzyme-2 (ACE2) for virus entry, SARS-CoV-2 is much more infectious than SARS-CoV. Structure-based sequence comparison of the N-terminal domain (NTD) of the spike protein of Middle East respiratory syndrome (MERS)-CoV, SARS-CoV, and SARS-CoV-2 illustrate three divergent loop regions in SARS-CoV-2, which is reminiscent of MERS-CoV sialoside binding pockets. Comparative binding analysis with host sialosides revealed conformational flexibility of SARS-CoV-2 divergent loop regions to accommodate diverse glycan-rich sialosides. These key differences with SARS-CoV and similarity with MERS-CoV suggest an evolutionary adaptation of SARS-CoV-2 spike glycoprotein reciprocal interaction with host surface sialosides to infect host cells with wide tissue tropism. |
topic |
SARS-CoV-2 N-terminal domain spike glycoprotein MERS-CoV |
url |
https://www.mdpi.com/1999-4915/12/9/909 |
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