Viruses traverse the human proteome through peptide interfaces that can be biomimetically leveraged for drug discovery.

ABSTRACT: We present a drug design strategy based on structural knowledge of protein-protein interfaces selected through virus-host coevolution and translated into highly potential small molecules. This approach is grounded on Vinland, the most comprehensive atlas of virus-human protein-protein interactions with annotation of interacting domains. From this inspiration, we identified small viral protein domains responsible for interaction with human proteins. These peptides form a library of new chemical entities used to screen for replication modulators of several pathogens. As a proof of concept, a peptide from a KSHV protein, identified as an inhibitor of influenza virus replication, was translated into a small molecule series with low nanomolar antiviral activity. By targeting the NEET proteins,

SUBMITTER: Meyniel-Schicklin L 

PROVIDER: S-EPMC10835127 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature