Stabilization of the SARS-CoV-2 receptor binding domain by protein core redesign and deep mutational scanning.

ABSTRACT: Stabilizing antigenic proteins as vaccine immunogens or diagnostic reagents is a stringent case of protein engineering and design as the exterior surface must maintain recognition by receptor(s) and antigen-specific antibodies at multiple distinct epitopes. This is a challenge, as stability enhancing mutations must be focused on the protein core, whereas successful computational stabilization algorithms typically select mutations at solvent-facing positions. In this study, we report the stabilization of SARS-CoV-2 Wuhan Hu-1 Spike receptor binding domain using a combination of deep mutational scanning and computational design, including the FuncLib algorithm. Our most successful design encodes I358F, Y365W, T430I, and I513L receptor binding domain mutations, maintains recognition by the re

SUBMITTER: Leonard AC 

PROVIDER: S-EPMC9077414 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature