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Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading SARS-CoV-2 Variants.
J Mol Biol. 2021 07 23; 433(15):167058.JM

Abstract

Rapidly spreading new variants of SARS-CoV-2 carry multiple mutations in the viral spike protein which attaches to the angiotensin converting enzyme 2 (ACE2) receptor on host cells. Among these mutations are amino acid changes N501Y (lineage B.1.1.7, first identified in the UK), and the combination N501Y, E484K, K417N (B.1.351, first identified in South Africa), all located at the interface on the receptor binding domain (RBD). We experimentally establish that RBD containing the N501Y mutation results in 7-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation only slightly enhances the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 2-fold weaker than N501Y. However, the recently emerging double mutant E484K/N501Y binds even stronger than N501Y. The independent evolution of lineages containing mutations with different effects on receptor binding affinity, viral transmission and immune evasion underscores the importance of global viral genome surveillance and functional characterization.

Authors+Show Affiliations

Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands; Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands. Electronic address: j.lebbink@erasmusmc.nl.

Pub Type(s)

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

Language

eng

PubMed ID

34023401

Citation

Laffeber, Charlie, et al. "Experimental Evidence for Enhanced Receptor Binding By Rapidly Spreading SARS-CoV-2 Variants." Journal of Molecular Biology, vol. 433, no. 15, 2021, p. 167058.
Laffeber C, de Koning K, Kanaar R, et al. Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading SARS-CoV-2 Variants. J Mol Biol. 2021;433(15):167058.
Laffeber, C., de Koning, K., Kanaar, R., & Lebbink, J. H. G. (2021). Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading SARS-CoV-2 Variants. Journal of Molecular Biology, 433(15), 167058. https://doi.org/10.1016/j.jmb.2021.167058
Laffeber C, et al. Experimental Evidence for Enhanced Receptor Binding By Rapidly Spreading SARS-CoV-2 Variants. J Mol Biol. 2021 07 23;433(15):167058. PubMed PMID: 34023401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading SARS-CoV-2 Variants. AU - Laffeber,Charlie, AU - de Koning,Kelly, AU - Kanaar,Roland, AU - Lebbink,Joyce H G, Y1 - 2021/05/21/ PY - 2021/04/06/received PY - 2021/05/15/revised PY - 2021/05/17/accepted PY - 2021/5/24/pubmed PY - 2021/7/22/medline PY - 2021/5/23/entrez KW - angiotensin converting enzyme 2 receptor KW - coronavirus KW - mutations KW - spike receptor binding domain KW - surface plasmon resonance SP - 167058 EP - 167058 JF - Journal of molecular biology JO - J Mol Biol VL - 433 IS - 15 N2 - Rapidly spreading new variants of SARS-CoV-2 carry multiple mutations in the viral spike protein which attaches to the angiotensin converting enzyme 2 (ACE2) receptor on host cells. Among these mutations are amino acid changes N501Y (lineage B.1.1.7, first identified in the UK), and the combination N501Y, E484K, K417N (B.1.351, first identified in South Africa), all located at the interface on the receptor binding domain (RBD). We experimentally establish that RBD containing the N501Y mutation results in 7-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation only slightly enhances the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 2-fold weaker than N501Y. However, the recently emerging double mutant E484K/N501Y binds even stronger than N501Y. The independent evolution of lineages containing mutations with different effects on receptor binding affinity, viral transmission and immune evasion underscores the importance of global viral genome surveillance and functional characterization. SN - 1089-8638 UR - https://www.unboundmedicine.com/medline/citation/34023401/Experimental_Evidence_for_Enhanced_Receptor_Binding_by_Rapidly_Spreading_SARS_CoV_2_Variants_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2836(21)00276-X DB - PRIME DP - Unbound Medicine ER -