Discovery of Non-Covalent Inhibitors for SARS-CoV-2 PLpro: Integrating Virtual Screening, Synthesis, and Experimental Validation.

ABSTRACT: The SARS-CoV-2 pandemic has significantly challenged global public health, highlighting the need for effective therapeutic options. This study focuses on the papain-like protease (PLpro) of SARS-CoV-2, which is a critical enzyme for viral polyprotein processing, maturation, and immune evasion. We employed a combined approach that began with computational models in a virtual screening campaign, prioritizing compounds from our in-house chemical library against PLpro. Out of 81 virtual hits evaluated through enzymatic and biophysical assays, we identified a modest inhibitor featuring a naphthyridine core with an IC₅₀ of 73.61 μM and a K _i of 22 μM. Expanding our exploration, we synthesized and assessed 30 naphthyridine analogues, three of which emerged as promisin

SUBMITTER: Sousa BKP 

PROVIDER: S-EPMC11647681 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature