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Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: Similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism.

Houcemeddine Othman1 Zied Bouslama2 Jean-Tristan Brandenburg3 Jorge da Rocha3 Yosr Hamdi4 Kais Ghedira5 Najet Srairi-Abid6 Scott Hazelhurst7,8
Affiliations 8 institutions
  1. Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: [email protected].
  2. Laboratory of Veterinary Epidemiology and Microbiology LR16IPT03, Institut Pasteur of Tunis. University of Tunis El Manar, Tunis, Tunisia.
  3. Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  4. Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.
  5. Laboratory of Bioinformatics, Biomathematics and Biostatistics, LR16IPT09, Pasteur Institute of Tunis, University Tunis El Manar, Tunis, Tunisia.
  6. Université de Tunis El Manar, Institut Pasteur de Tunis, LR11IPT08 Venins et Biomolécules Thérapeutiques, 1002, Tunis, Tunisia.
  7. Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  8. School of Electrical and Information Engineering, University of the Witwatersrand, Johannesburg, South Africa.
PMID 32410735 2020 Biochem Biophys Res Commun eng ppublish
PubMed DOI Browse context

Article

Publication summary

The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.

ACE2 COVID-19 Homology-based protein-protein docking Variants Viral spike receptor binding domain Amino Acid Sequence Angiotensin-Converting Enzyme 2 Betacoronavirus Binding Sites Coronavirus Infections COVID-19 Humans Molecular Docking Simulation Pandemics Peptidyl-Dipeptidase A Phylogeny Pneumonia, Viral Protein Domains

Structured evidence records

Evidence records

3 total
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.75
Key finding

Phylogenetic analysis indicates that the spike protein RBD interface of SARS-CoV-2 was likely acquired through a complex evolutionary process, highlighting genomic evolution relative to SARS-CoV.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations.

Genes or proteins
spike; RBD
Analysis methods
phylogenetic analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.85
Key finding

Q493 and P499 residues in the SARS-CoV-2 spike receptor-binding domain enhance binding affinity and stability with human ACE2, supporting molecular adaptation for efficient host receptor interaction.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

We highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface.

Genes or proteins
spike; RBD
Receptors
ACE2
Mutations
Q493; P499
Mechanism types
receptor_binding; host_adaptation
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.95
Key finding

SARS-CoV-2 spike RBD binds to human ACE2 as the entry receptor; structural and binding assays confirm ACE2-mediated cell entry and identify critical residues Q493 and P499 involved in the interaction.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. We provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2.

Method
protein-protein binding assay; structural analysis; molecular docking simulation
Receptors
ACE2