Mutational effects on ACE2-binding affinity and expression in SARS-CoV-2 variant RBDs


Overview

You can use this tool to explore the experimentally determined impacts of amino acid mutations on ACE2-binding affinity and expression in SARS-CoV-2 receptor-binding domain (RBD) variants.

Instruction

To use this tool, select the RBD variants that you wish to display in each heatmap by selecting a variant from the drop down menu corresponding to each plot. Then, you can select the metric that you wish to display in the heatmap (either change in ACE2 binding affinity (-log10 \(K_D\)), or change in RBD expression (log(MFI)) by selecting that metric in the corresponding drop down menu. Hover over individual mutations to see exact numerical details.

Technical Details

The impact on ACE2 receptor-binding affinity (\(\Delta\) log10 \(K_D\)) or RBD expression (\(\Delta\) log(MFI)) of every single amino-acid mutation in SARS-CoV-2 RBDs, as determined by high-throughput titration assays. Wildtype amino acids are indicated by an ‘x’, and gray squares indicate missing mutations from each library. The number of internally replicated barcodes with which a mutation was measured is visible as Barcode Count in the tooltips, where higher numbers indicate higher-confidence measurements. The experiments underlying these data can be found in our preprint here.

Data labeled “v1” (Alpha, Beta, Delta, Eta, and associated Wuhan-Hu-1 v1 measurements) are from a previously published study described here. The Wuhan-Hu-1 library was also spiked into the Omicron BA.1 and BA.2 libraries in a separate experiment. Although each Wuhan-Hu-1 dataset is closely correlated, it is most appropriate to compare each variant dataset to its matched Wuhan-Hu-1 dataset due to internal control.

Data

Raw data can be found here. The code used to make these plots can be found here.