The study results showed that all the 32,768 SARS-CoV-2 RBD intermediates possible between the Wuhan strain and the Omicron BA.1 variant had a detectable affinity toward ACE2 with a K D,app between 0.1 μM and 0.1 nM. Furthermore, a standard biochemical model of epistasis was fit for the study data. The team used a method based on sequencing and high-throughput flow cytometry called Tite-Seq to estimate the binding affinities (K D,app) of all the possible viral RBD variants to the human ACE2. This library included all the evolutionary intermediates possible between the BA.1 and the Wuhan RBDs. The team employed a combinatorial assembly approach to develop a plasmid library comprising all probable combinations of the 15 mutations observed in the BA.1 RBD. In the present study, researchers mapped the epistatic interactions incident between mutations present in the receptor-binding domain of the SARS-CoV-2 Omicron BA.1 sublineage compared to those in the Wuhan strain. However, extensive research is required to understand the interactions between combinations of mutations found in Omicron and their impact on immune evasion and ACE2 affinity. These studies focus on the impact of single mutations on only particular genetic backgrounds. Various studies have investigated the effects of mutations in the SARS-CoV-2 Omicron variant on ACE2 affinity as well as antibody binding.

Image Credit: Kateryna Kon/Shutterstock Background Study: Compensatory epistasis maintains ACE2 affinity in SARS-CoV-2 Omicron BA.1. In a recent study posted to the bioRxiv* preprint server, researchers assessed the impact of epistatic interactions on the angiotensin-converting enzyme-2 (ACE2) affinity in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. By Bhavana Kunkalikar Reviewed by Danielle Ellis, B.Sc.

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