Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading SARS-CoV-2 Variants

Charlie Laffeber, Kelly de Koning, Roland Kanaar, Joyce H.G. Lebbink*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

106 Citations (Scopus)

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.

Original languageEnglish
Article number167058
JournalJournal of Molecular Biology
Volume433
Issue number15
DOIs
Publication statusPublished - 23 Jul 2021

Bibliographical note

Funding Information:
We are grateful to Bart Haagmans and Marion Koopmans for valuable comments and critical reading of the manuscript. We are grateful for infrastructural support from the Josephine Nefkens Precision Cancer Treatment Program. Funding: this work is supported by the gravitation program CancerGenomiCs.nl from the Netherlands Organisation for Scientific Research (NWO), part of the Oncode Institute, which is partly financed by the Dutch Cancer Society, and NWO grant OCENW.XS.055.

Publisher Copyright:
© 2021 The Author(s)

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