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Structural genetics of circulating variants affecting the SARS-CoV-2 spike/human ACE2 complex.
J Biomol Struct Dyn. 2022 09; 40(14):6545-6555.JB

Abstract

SARS-CoV-2 entry in human cells is mediated by the interaction between the viral Spike protein and the human ACE2 receptor. This mechanism evolved from the ancestor bat coronavirus and is currently one of the main targets for antiviral strategies. However, there currently exist several Spike protein variants in the SARS-CoV-2 population as the result of mutations, and it is unclear if these variants may exert a specific effect on the affinity with ACE2 which, in turn, is also characterized by multiple alleles in the human population. In the current study, the GBPM analysis, originally developed for highlighting host-guest interaction features, has been applied to define the key amino acids responsible for the Spike/ACE2 molecular recognition, using four different crystallographic structures. Then, we intersected these structural results with the current mutational status, based on more than 295,000 sequenced cases, in the SARS-CoV-2 population. We identified several Spike mutations interacting with ACE2 and mutated in at least 20 distinct patients: S477N, N439K, N501Y, Y453F, E484K, K417N, S477I and G476S. Among these, mutation N501Y in particular is one of the events characterizing SARS-CoV-2 lineage B.1.1.7, which has recently risen in frequency in Europe. We also identified five ACE2 rare variants that may affect interaction with Spike and susceptibility to infection: S19P, E37K, M82I, E329G and G352V.Communicated by Ramaswamy H. Sarma.

Authors+Show Affiliations

Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy. Net4Science srl, c/o University "Magna Graecia" of Catanzaro, Catanzaro, Italy.Department of Surgical and Medical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.Department of Surgical and Medical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33583326

Citation

Ortuso, Francesco, et al. "Structural Genetics of Circulating Variants Affecting the SARS-CoV-2 Spike/human ACE2 Complex." Journal of Biomolecular Structure & Dynamics, vol. 40, no. 14, 2022, pp. 6545-6555.
Ortuso F, Mercatelli D, Guzzi PH, et al. Structural genetics of circulating variants affecting the SARS-CoV-2 spike/human ACE2 complex. J Biomol Struct Dyn. 2022;40(14):6545-6555.
Ortuso, F., Mercatelli, D., Guzzi, P. H., & Giorgi, F. M. (2022). Structural genetics of circulating variants affecting the SARS-CoV-2 spike/human ACE2 complex. Journal of Biomolecular Structure & Dynamics, 40(14), 6545-6555. https://doi.org/10.1080/07391102.2021.1886175
Ortuso F, et al. Structural Genetics of Circulating Variants Affecting the SARS-CoV-2 Spike/human ACE2 Complex. J Biomol Struct Dyn. 2022;40(14):6545-6555. PubMed PMID: 33583326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural genetics of circulating variants affecting the SARS-CoV-2 spike/human ACE2 complex. AU - Ortuso,Francesco, AU - Mercatelli,Daniele, AU - Guzzi,Pietro Hiram, AU - Giorgi,Federico Manuel, Y1 - 2021/02/13/ PY - 2021/2/16/pubmed PY - 2022/8/24/medline PY - 2021/2/15/entrez KW - ACE2 KW - COVID-19 KW - SARS-CoV-2 KW - mutations KW - spike SP - 6545 EP - 6555 JF - Journal of biomolecular structure & dynamics JO - J Biomol Struct Dyn VL - 40 IS - 14 N2 - SARS-CoV-2 entry in human cells is mediated by the interaction between the viral Spike protein and the human ACE2 receptor. This mechanism evolved from the ancestor bat coronavirus and is currently one of the main targets for antiviral strategies. However, there currently exist several Spike protein variants in the SARS-CoV-2 population as the result of mutations, and it is unclear if these variants may exert a specific effect on the affinity with ACE2 which, in turn, is also characterized by multiple alleles in the human population. In the current study, the GBPM analysis, originally developed for highlighting host-guest interaction features, has been applied to define the key amino acids responsible for the Spike/ACE2 molecular recognition, using four different crystallographic structures. Then, we intersected these structural results with the current mutational status, based on more than 295,000 sequenced cases, in the SARS-CoV-2 population. We identified several Spike mutations interacting with ACE2 and mutated in at least 20 distinct patients: S477N, N439K, N501Y, Y453F, E484K, K417N, S477I and G476S. Among these, mutation N501Y in particular is one of the events characterizing SARS-CoV-2 lineage B.1.1.7, which has recently risen in frequency in Europe. We also identified five ACE2 rare variants that may affect interaction with Spike and susceptibility to infection: S19P, E37K, M82I, E329G and G352V.Communicated by Ramaswamy H. Sarma. SN - 1538-0254 UR - https://www.unboundmedicine.com/medline/citation/33583326/Structural_genetics_of_circulating_variants_affecting_the_SARS_CoV_2_spike/human_ACE2_complex_ L2 - https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1886175 DB - PRIME DP - Unbound Medicine ER -