Tags

Type your tag names separated by a space and hit enter

Probing structural basis for enhanced binding of SARS-CoV-2 P.1 variant spike protein with the human ACE2 receptor.
J Cell Biochem. 2022 07; 123(7):1207-1221.JC

Abstract

The initial step of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves the binding of receptor binding domain (RBD) of the spike protein to the angiotensin converting enzyme 2 (ACE2) receptor. Each successive wave of SARS-CoV-2 reports emergence of many new variants, which is associated with mutations in the RBD as well as other parts of the spike protein. These mutations are reported to have enhanced affinity towards the ACE2 receptor as well as are also crucial for the virus transmission. Many computational and experimental studies have demonstrated the effect of individual mutation on the RBD-ACE2 binding. However, the cumulative effect of mutations on the RBD and away from the RBD was not investigated in detail. We report here a comparative analysis on the structural communication and dynamics of the RBD and truncated S1 domain of spike protein in complex with the ACE2 receptor from SARS-CoV-2 wild type and its P.1 variant. Our integrative network and dynamics approaches highlighted a subtle conformational changes in the RBD as well as truncated S1 domain of spike protein at the protein contact level, responsible for the increased affinity with the ACE2 receptor. Moreover, our study also identified the commonalities and differences in the dynamics of the interactions between spike protein of SARS-CoV-2 wild type and its P.1 variant with the ACE2 receptor. Further, our investigation yielded an understanding towards identification of the unique RBD residues crucial for the interaction with the ACE2 host receptor. Overall, the study provides an insight for designing better therapeutics against the circulating P.1 variants as well as other future variants.

Authors+Show Affiliations

Laboratory of Structural Biology, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.Laboratory of Structural Biology, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35620980

Citation

Lata, Surabhi, and Mohd Akif. "Probing Structural Basis for Enhanced Binding of SARS-CoV-2 P.1 Variant Spike Protein With the Human ACE2 Receptor." Journal of Cellular Biochemistry, vol. 123, no. 7, 2022, pp. 1207-1221.
Lata S, Akif M. Probing structural basis for enhanced binding of SARS-CoV-2 P.1 variant spike protein with the human ACE2 receptor. J Cell Biochem. 2022;123(7):1207-1221.
Lata, S., & Akif, M. (2022). Probing structural basis for enhanced binding of SARS-CoV-2 P.1 variant spike protein with the human ACE2 receptor. Journal of Cellular Biochemistry, 123(7), 1207-1221. https://doi.org/10.1002/jcb.30276
Lata S, Akif M. Probing Structural Basis for Enhanced Binding of SARS-CoV-2 P.1 Variant Spike Protein With the Human ACE2 Receptor. J Cell Biochem. 2022;123(7):1207-1221. PubMed PMID: 35620980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Probing structural basis for enhanced binding of SARS-CoV-2 P.1 variant spike protein with the human ACE2 receptor. AU - Lata,Surabhi, AU - Akif,Mohd, Y1 - 2022/05/27/ PY - 2022/04/22/revised PY - 2022/01/21/received PY - 2022/05/10/accepted PY - 2022/5/28/pubmed PY - 2022/7/20/medline PY - 2022/5/27/entrez KW - ACE2 receptor KW - COVID-19 KW - SARS-CoV-2 KW - molecular dynamic simulation KW - protein network analysis KW - spike protein KW - variant SP - 1207 EP - 1221 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 123 IS - 7 N2 - The initial step of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves the binding of receptor binding domain (RBD) of the spike protein to the angiotensin converting enzyme 2 (ACE2) receptor. Each successive wave of SARS-CoV-2 reports emergence of many new variants, which is associated with mutations in the RBD as well as other parts of the spike protein. These mutations are reported to have enhanced affinity towards the ACE2 receptor as well as are also crucial for the virus transmission. Many computational and experimental studies have demonstrated the effect of individual mutation on the RBD-ACE2 binding. However, the cumulative effect of mutations on the RBD and away from the RBD was not investigated in detail. We report here a comparative analysis on the structural communication and dynamics of the RBD and truncated S1 domain of spike protein in complex with the ACE2 receptor from SARS-CoV-2 wild type and its P.1 variant. Our integrative network and dynamics approaches highlighted a subtle conformational changes in the RBD as well as truncated S1 domain of spike protein at the protein contact level, responsible for the increased affinity with the ACE2 receptor. Moreover, our study also identified the commonalities and differences in the dynamics of the interactions between spike protein of SARS-CoV-2 wild type and its P.1 variant with the ACE2 receptor. Further, our investigation yielded an understanding towards identification of the unique RBD residues crucial for the interaction with the ACE2 host receptor. Overall, the study provides an insight for designing better therapeutics against the circulating P.1 variants as well as other future variants. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/35620980/Probing_structural_basis_for_enhanced_binding_of_SARS_CoV_2_P_1_variant_spike_protein_with_the_human_ACE2_receptor_ DB - PRIME DP - Unbound Medicine ER -