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[Preprint]. 2021 Feb 22:2021.02.22.432359.
doi: 10.1101/2021.02.22.432359.

SARS-CoV-2 B.1.1.7 and B.1.351 Spike variants bind human ACE2 with increased affinity

Affiliations

SARS-CoV-2 B.1.1.7 and B.1.351 Spike variants bind human ACE2 with increased affinity

Muthukumar Ramanathan et al. bioRxiv. .

Update in

Abstract

SARS-CoV2 being highly infectious has been particularly effective in causing widespread infection globally and more variants of SARS-CoV2 are constantly being reported with increased genomic surveillance. In particular, the focus is on mutations of Spike protein, which binds human ACE2 protein enabling SARS-CoV2 entry and infection. Here we present a rapid experimental method leveraging the speed and flexibility of Mircoscale Thermopheresis (MST) to characterize the interaction between Spike Receptor Binding Domain (RBD) and human ACE2 protein. The B.1.351 variant harboring three mutations, (E484K, N501Y, and K417N) binds the ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD. We also find that the B.1.1.7 variant, binds two-fold more tightly to ACE2 than the SARS-COV-2 RBD.

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Figures

Fig. 1
Fig. 1. Binding of SARS-CoV-2 Spike RBD with Human ACE2
Microscale thermophoresis with 100nM labeled Spike RBD (A) Binding curve of SCoV2 and B.1.1.7 RBD with a titration series of human ACE2 (n=3 series of independent replicates) (B) Binding curve of SCoV2 and B.1.351 RBD with a titration series of human ACE2 (n=3 series of independent replicates).

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