Computational design and engineering of self-assembling multivalent microproteins with therapeutic potential against SARS-CoV-2.

ABSTRACT: Multivalent drugs targeting homo-oligomeric viral surface proteins, such as the SARS-CoV-2 trimeric spike (S) protein, have the potential to elicit more potent and broad-spectrum therapeutic responses than monovalent drugs by synergistically engaging multiple binding sites on viral targets. However, rational design and engineering of nanoscale multivalent protein drugs are still lacking. Here, we developed a computational approach to engineer self-assembling trivalent microproteins that simultaneously bind to the three receptor binding domains (RBDs) of the S protein. This approach involves four steps: structure-guided linker design, molecular simulation evaluation of self-assembly, experimental validation of self-assembly state, and functional testing. Using this approach, we first design

SUBMITTER: Qin Q 

PROVIDER: S-EPMC10858482 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature