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Receptor binding domain of SARS-CoV-2 from Wuhan strain to Omicron B.1.1.529 attributes increased affinity to variable structures of human ACE2.
J Infect Public Health. 2022 Jul; 15(7):781-787.JI

Abstract

BACKGROUND

COVID-19 is an infectious disease declared as a global pandemic caused by SARS-CoV-2 virus. Genomic changes in the receptor binding domain (RBD) region of SARS-CoV-2 led to an increased, infectivity in humans through interaction with the angiotensin-converting enzyme2 (ACE2) receptor. Simultaneously, the genetic variants in ACE2 provide an opportunity for SARS-CoV-2 infection and severity. We demonstrate the binding efficiencies of RBDs of SARS-CoV-2 strain with ACE2 variants of the human host.

METHODOLOGY

A Total of 615 SARS-CoV-2 genomes were retrieved from repository. Eighteen variations were identified contributing to structural changes in RBD that are distributed in 615 isolates. An analyses of 285 single nucleotide variances at the coding region of the ACE2 receptor showed 34 to be pathogenic. Homology models of 34 ACE2 and 18 RBD structures were constructed with 34 and 18 structural variants, respectively. Protein docking of 612 (34 *18) ACE2-RBD complexes showed variable affinities compared to wildtype Wuhan's and other SARS-CoV-2 RBDs, including Omicron B.1.1.529. Finally, molecular dynamic simulation was performed to determine the stability of the complexes.

RESULTS

Among 612, the top 3 complexes showing least binding energy were selected. The ACE2 with rs961360700 variant showed the least binding energy (-895.2 Kcal/mol) on binding with the RBD of Phe160Ser variant compared to Wuhan's RBD complex. Interestingly, the binding energy of RBD of Omicron B.1.1.529 with ACE2 (rs961360700) structure showed least binding energy of -1010 Kcal/mol. Additionally, molecular dynamics showed structure stability for all the analysed complexes with the RMSD (0.22-0.26 nm), RMSF (0.11-0.13 nm), and Rg (2.53-2.56 nm).

CONCLUSION

In conclusion, our investigation highlights the clinical variants contributing to structural variants in ACE2 receptors that lead to efficient binding of SARS-CoV-2. Therefore, screening of these ACE2 polymorphisms will help detect COVID-19 risk population so as to provide additional care and for safe management.

Authors+Show Affiliations

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia; Centre of Molecular Medicine and Diagnostics (COMManD), Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 600077, India. Electronic address: dr.ravipatil@gmail.com.Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia.Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia.Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia.Department of Physical Therapy, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia.Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences,University of Tabuk, Tabuk 71491, Saudi Arabia.Department of Biotechnology, College of Science, Taif University, Taif 21944, Saudi Arabia.College of Nursing, Jazan University, Jazan 45412, Saudi Arabia.Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia.Department of Restorative Dental Sciences, Division of Operative Dentistry, College of dentistry, Jazan University, Jazan 45412, Saudi Arabia; Department of Cariology. Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 600077, India.Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai 600130, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35738053

Citation

Patil, Shankargouda, et al. "Receptor Binding Domain of SARS-CoV-2 From Wuhan Strain to Omicron B.1.1.529 Attributes Increased Affinity to Variable Structures of Human ACE2." Journal of Infection and Public Health, vol. 15, no. 7, 2022, pp. 781-787.
Patil S, Alzahrani KJ, Banjer HJ, et al. Receptor binding domain of SARS-CoV-2 from Wuhan strain to Omicron B.1.1.529 attributes increased affinity to variable structures of human ACE2. J Infect Public Health. 2022;15(7):781-787.
Patil, S., Alzahrani, K. J., Banjer, H. J., Halawani, I. F., Alzahrani, H., Altayar, M. A., Albogami, S., Angeles, R. F., Hassan, A. A. A., Bhandi, S., & Raj, A. T. (2022). Receptor binding domain of SARS-CoV-2 from Wuhan strain to Omicron B.1.1.529 attributes increased affinity to variable structures of human ACE2. Journal of Infection and Public Health, 15(7), 781-787. https://doi.org/10.1016/j.jiph.2022.06.004
Patil S, et al. Receptor Binding Domain of SARS-CoV-2 From Wuhan Strain to Omicron B.1.1.529 Attributes Increased Affinity to Variable Structures of Human ACE2. J Infect Public Health. 2022;15(7):781-787. PubMed PMID: 35738053.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Receptor binding domain of SARS-CoV-2 from Wuhan strain to Omicron B.1.1.529 attributes increased affinity to variable structures of human ACE2. AU - Patil,Shankargouda, AU - Alzahrani,Khalid J, AU - Banjer,Hamsa Jameel, AU - Halawani,Ibrahim Faisal, AU - Alzahrani,Hosam, AU - Altayar,Malik A, AU - Albogami,Sarah, AU - Angeles,Robert Fua, AU - Hassan,Ali Abdel-Halim Abdel-Azim, AU - Bhandi,Shilpa, AU - Raj,A Thirumal, Y1 - 2022/06/16/ PY - 2022/04/05/received PY - 2022/06/08/revised PY - 2022/06/12/accepted PY - 2022/6/24/pubmed PY - 2022/7/7/medline PY - 2022/6/23/entrez KW - Angiotensin-converting enzyme KW - Dynamic simulation KW - Omicron KW - Protein docking KW - Receptor binding domain KW - SARS‐CoV‐2 SP - 781 EP - 787 JF - Journal of infection and public health JO - J Infect Public Health VL - 15 IS - 7 N2 - BACKGROUND: COVID-19 is an infectious disease declared as a global pandemic caused by SARS-CoV-2 virus. Genomic changes in the receptor binding domain (RBD) region of SARS-CoV-2 led to an increased, infectivity in humans through interaction with the angiotensin-converting enzyme2 (ACE2) receptor. Simultaneously, the genetic variants in ACE2 provide an opportunity for SARS-CoV-2 infection and severity. We demonstrate the binding efficiencies of RBDs of SARS-CoV-2 strain with ACE2 variants of the human host. METHODOLOGY: A Total of 615 SARS-CoV-2 genomes were retrieved from repository. Eighteen variations were identified contributing to structural changes in RBD that are distributed in 615 isolates. An analyses of 285 single nucleotide variances at the coding region of the ACE2 receptor showed 34 to be pathogenic. Homology models of 34 ACE2 and 18 RBD structures were constructed with 34 and 18 structural variants, respectively. Protein docking of 612 (34 *18) ACE2-RBD complexes showed variable affinities compared to wildtype Wuhan's and other SARS-CoV-2 RBDs, including Omicron B.1.1.529. Finally, molecular dynamic simulation was performed to determine the stability of the complexes. RESULTS: Among 612, the top 3 complexes showing least binding energy were selected. The ACE2 with rs961360700 variant showed the least binding energy (-895.2 Kcal/mol) on binding with the RBD of Phe160Ser variant compared to Wuhan's RBD complex. Interestingly, the binding energy of RBD of Omicron B.1.1.529 with ACE2 (rs961360700) structure showed least binding energy of -1010 Kcal/mol. Additionally, molecular dynamics showed structure stability for all the analysed complexes with the RMSD (0.22-0.26 nm), RMSF (0.11-0.13 nm), and Rg (2.53-2.56 nm). CONCLUSION: In conclusion, our investigation highlights the clinical variants contributing to structural variants in ACE2 receptors that lead to efficient binding of SARS-CoV-2. Therefore, screening of these ACE2 polymorphisms will help detect COVID-19 risk population so as to provide additional care and for safe management. SN - 1876-035X UR - https://www.unboundmedicine.com/medline/citation/35738053/Receptor_binding_domain_of_SARS_CoV_2_from_Wuhan_strain_to_Omicron_B_1_1_529_attributes_increased_affinity_to_variable_structures_of_human_ACE2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1876-0341(22)00150-2 DB - PRIME DP - Unbound Medicine ER -