Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution

Overview

SARS-CoV-2 has evolved variants with substitutions in the spike receptor-binding domain (RBD) that impact its affinity for ACE2 receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the impact on ACE2 binding of all single amino-acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs.

Here, we link to two interactive visualizations that enable exploration of the data from these deep mutational scans across SARS_CoV-2 variants. The manuscript detailing the results of these experiments is published here.

Instructions

We have made two tools to help visualize the data from our deep mutational scans:

  1. A set of interactive heatmaps that you can use to explore the change in ACE2-binding affinity (\(\Delta\)log10 \(K_D\)) or the change in RBD expression (log10(MFI)) caused by mutations in each RBD variant. To use this tool, click here.

  2. An interactive widget that you can use to visualize epistatic shifts in mutational effects on ACE2-binding affinity (-log10 \(K_D\)) between variant RBDs. To use this tool, click here.

Data

If you are interested in the raw data from our study, you can find the ACE2-binding affinity (-log10 \(K_D\)) and RBD expression (log10(MFI)) measurements from each experiment here. You can find the data used to plot the epistatic shifts between variant backgrounds here.