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Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein.
J Med Virol. 2020 Sep; 92(9):1580-1586.JM

Abstract

The recent pandemic of COVID-19, caused by SARS-CoV-2, is unarguably the most fearsome compared with the earlier outbreaks caused by other coronaviruses, SARS-CoV and MERS-CoV. Human ACE2 is now established as a receptor for the SARS-CoV-2 spike protein. Where variations in the viral spike protein, in turn, lead to the cross-species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS-CoV-2 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. The models were then superimposed over the native ACE2 and ACE2-spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS-CoV-2 spike protein, respectively. Despite strong overall structural similarities, the spatial orientation of the key interacting residues varies in the ACE2 variants compared with the wild-type molecule. Most ACE2 variants showed a similar binding affinity for SARS-CoV-2 spike protein as observed in the complex structure of wild-type ACE2 and SARS-CoV-2 spike protein. However, ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein. In summary, our data provide a structural basis of potential resistance against SARS-CoV-2 infection driven by ACE2 allelic variants.

Authors+Show Affiliations

Bioinformatics and Molecular Medicine Research Group, Dow Research Institute of Biotechnology and Biomedical Sciences, Dow College of Biotechnology, Dow University of Health Sciences, Karachi, Pakistan.Department of Microbiology, University of Karachi, Karachi, Pakistan.Bioinformatics and Molecular Medicine Research Group, Dow Research Institute of Biotechnology and Biomedical Sciences, Dow College of Biotechnology, Dow University of Health Sciences, Karachi, Pakistan.Bioinformatics and Molecular Medicine Research Group, Dow Research Institute of Biotechnology and Biomedical Sciences, Dow College of Biotechnology, Dow University of Health Sciences, Karachi, Pakistan. Department of Microbiology, University of Karachi, Karachi, Pakistan.Bioinformatics and Molecular Medicine Research Group, Dow Research Institute of Biotechnology and Biomedical Sciences, Dow College of Biotechnology, Dow University of Health Sciences, Karachi, Pakistan.Bioinformatics and Molecular Medicine Research Group, Dow Research Institute of Biotechnology and Biomedical Sciences, Dow College of Biotechnology, Dow University of Health Sciences, Karachi, Pakistan.Bioinformatics and Molecular Medicine Research Group, Dow Research Institute of Biotechnology and Biomedical Sciences, Dow College of Biotechnology, Dow University of Health Sciences, Karachi, Pakistan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32249956

Citation

Hussain, Mushtaq, et al. "Structural Variations in Human ACE2 May Influence Its Binding With SARS-CoV-2 Spike Protein." Journal of Medical Virology, vol. 92, no. 9, 2020, pp. 1580-1586.
Hussain M, Jabeen N, Raza F, et al. Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein. J Med Virol. 2020;92(9):1580-1586.
Hussain, M., Jabeen, N., Raza, F., Shabbir, S., Baig, A. A., Amanullah, A., & Aziz, B. (2020). Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein. Journal of Medical Virology, 92(9), 1580-1586. https://doi.org/10.1002/jmv.25832
Hussain M, et al. Structural Variations in Human ACE2 May Influence Its Binding With SARS-CoV-2 Spike Protein. J Med Virol. 2020;92(9):1580-1586. PubMed PMID: 32249956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein. AU - Hussain,Mushtaq, AU - Jabeen,Nusrat, AU - Raza,Fozia, AU - Shabbir,Sanya, AU - Baig,Ayesha A, AU - Amanullah,Anusha, AU - Aziz,Basma, Y1 - 2020/04/15/ PY - 2020/03/20/received PY - 2020/03/31/accepted PY - 2020/4/7/pubmed PY - 2020/12/29/medline PY - 2020/4/7/entrez KW - ACE2 KW - COVID-19 KW - SARS-CoV-2 KW - spike protein SP - 1580 EP - 1586 JF - Journal of medical virology JO - J Med Virol VL - 92 IS - 9 N2 - The recent pandemic of COVID-19, caused by SARS-CoV-2, is unarguably the most fearsome compared with the earlier outbreaks caused by other coronaviruses, SARS-CoV and MERS-CoV. Human ACE2 is now established as a receptor for the SARS-CoV-2 spike protein. Where variations in the viral spike protein, in turn, lead to the cross-species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS-CoV-2 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. The models were then superimposed over the native ACE2 and ACE2-spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS-CoV-2 spike protein, respectively. Despite strong overall structural similarities, the spatial orientation of the key interacting residues varies in the ACE2 variants compared with the wild-type molecule. Most ACE2 variants showed a similar binding affinity for SARS-CoV-2 spike protein as observed in the complex structure of wild-type ACE2 and SARS-CoV-2 spike protein. However, ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein. In summary, our data provide a structural basis of potential resistance against SARS-CoV-2 infection driven by ACE2 allelic variants. SN - 1096-9071 UR - https://www.unboundmedicine.com/medline/citation/32249956/Structural_variations_in_human_ACE2_may_influence_its_binding_with_SARS_CoV_2_spike_protein_ DB - PRIME DP - Unbound Medicine ER -