Literature detail

The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor.

Esther S Brielle^1,2 Dina Schneidman-Duhovny^1,3 Michal Linial¹

Affiliations 3 institutions

Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
The Alexander Grass Center for Bioengineering, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.

PMID 32365751 2020 Viruses eng epublish

Article

Publication summary

The COVID-19 disease has plagued over 200 countries with over three million cases and has resulted in over 200,000 deaths within 3 months. To gain insight into the high infection rate of the SARS-CoV-2 virus, we compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2-ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to the SARS-CoV-ACE2 complex. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications for therapeutic strategies.

ACE2 coronavirus evolution molecular dynamics protein–protein complex SARS-CoV-2 virus–host interactions Receptors, Virus Angiotensin-Converting Enzyme 2 Betacoronavirus Coronavirus NL63, Human Humans Molecular Dynamics Simulation Peptidyl-Dipeptidase A Protein Domains SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus Spike Glycoprotein, Coronavirus ACE2 protein, human

Structured evidence records

Evidence records

4 total

Receptor Usage 3 records

Receptor Usage Extraction confidence 1.00

Key finding

SARS-CoV-2 binds the human ACE2 receptor through a distinctive binding interface compared with SARS-CoV and HCoV-NL63, all recognizing ACE2 as their natural receptor.

Virus

Host

Location

Supporting text

We compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts.

Method: molecular dynamics simulation
Receptors: ACE2

Receptor Usage Extraction confidence 0.95

Key finding

SARS-CoV binds the human ACE2 receptor with comparable affinity to SARS-CoV-2 but via a different binding interface and residue contact network.

Virus

Host

Location

Supporting text

SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts.

Method: molecular dynamics simulation
Receptors: ACE2

Receptor Usage Extraction confidence 0.90

Key finding

Human coronavirus HCoV-NL63 also uses ACE2 as its receptor but exhibits a distinct binding interface compared to SARS-CoV and SARS-CoV-2.

Virus

Host

Location

Supporting text

SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts.

Method: molecular dynamics simulation
Receptors: ACE2

Molecular Adaptation 1 records

Molecular Adaptation Extraction confidence 0.90

Key finding

SARS-CoV-2 spike protein exhibits a distinct binding interface and residue contact network with human ACE2 compared to other ACE2-using coronaviruses, indicating molecular adaptation in receptor binding.

Virus

Host

Location

Supporting text

We compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses... SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts.

Genes or proteins: spike
Receptors: ACE2
Mechanism types: receptor_binding; cell_entry

Citation context

References

32 references

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Evidence overview

Evidence 4

Types 2

Virus 3

Host 1

Evidence types

Receptor Usage 3 Molecular Adaptation 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: Viruses
Volume / Issue / Pages: 12 / 5 / -
ISSN: 1999-4915
Journal country: Switzerland
DOI: 10.3390/v12050497