S375F mutation in Omicron variants causes destabilization and low production yield of SARS-CoV-2 recombinant Spike proteins.

Authors

Matthew Drew, Hannah Ambrose, Zoe Putman, Chao Yan Liu, Sarah Richards, Jonathan Zmuda, Vanessa Wall, Dominic Esposito

Published in

Protein expression and purification. Pages 107024. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

Omicron variants of the SARS-CoV-2 Spike protein have been challenging to produce recombinantly at high yields compared to their wild type counterparts. Using a variety of mutants within the receptor-binding domain of Spike, we have been able to identify a specific mutation, S375F, in Omicron variants which leads to the reduced protein production yields, likely due to decreased expression and reduced protein stability. In addition to revertant mutations which can improve the yield of Omicron proteins, we also demonstrate that a new HEK293 expression system, Gibco™ Expi293™ PRO, can restore higher yield for these challenging variants, eliminating the need for additional mutations.

PMID:
42833500
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.

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