An integrated understanding of the evolutionary and structural features of the SARS-CoV-2 spike receptor binding domain (RBD).

ABSTRACT: Conventional drug development strategies typically use pocket in protein structures as drug-target sites. They overlook the plausible effects of protein evolvability and resistant mutations on protein structure which in turn may impair protein-drug interaction. In this study, we used an integrated evolution and structure guided strategy to develop potential evolutionary-escape resistant therapeutics using receptor binding domain (RBD) of SARS-CoV-2 spike-protein/S-protein as a model. Deploying an ensemble of sequence space exploratory tools including co-evolutionary analysis and deep mutational scans we provide a quantitative insight into the evolutionarily constrained subspace of the RBD sequence-space. Guided by molecular simulation and structure network analysis we highlight regions ins

SUBMITTER: Sanyal D 

PROVIDER: S-EPMC9278002 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature