The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoV

• Published in: Viruses Vol. 12; no. 9; p. 909
• Main Authors: Awasthi, Mayanka, Gulati, Sahil, Sarkar, Debi P, Tiwari, Swasti, Kateriya, Suneel, Ranjan, Peeyush, Verma, Santosh Kumar
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19-08-2020; MDPI
• Subjects: ACE2; Amino Sugars - metabolism; Angiotensin; Angiotensin-converting enzyme 2; Betacoronavirus - chemistry; Betacoronavirus - physiology; Binding Sites; Communication; Coronaviruses; COVID-19; Divergence; Glycoproteins; Infections; Ligands; MERS-CoV; Microscopy; Middle East respiratory syndrome; Middle East Respiratory Syndrome Coronavirus - chemistry; Models, Molecular; Molecular Docking Simulation; Molecular Dynamics Simulation; N-Acetylneuraminic Acid - metabolism; N-terminal domain; Pandemics; Peptidyl-dipeptidase A; Phylogenetics; Protein Binding; Protein Domains; Protein structure; Proteins; Receptors, Coronavirus; Receptors, Virus - chemistry; Receptors, Virus - metabolism; Respiratory diseases; Respiratory system; SARS Virus - chemistry; SARS-CoV-2; Secondary infection; Severe acute respiratory syndrome coronavirus 2; Sialic Acids - metabolism; Sialyl Lewis X Antigen - metabolism; Simulation; Spike glycoprotein; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Standard deviation; Therapeutic applications; Tropism; Viral Tropism; Virus Internalization; SARS-CoV-2; MERS-CoV; spike glycoprotein; N-terminal domain
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v12090909

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.