Support Vector Machine Identification of Small Molecule Binders to an Understudied Allosteric Site of SARS-CoV-2 Mpro for Next-Generation PROTAC-Based Therapeutics.

ABSTRACT: The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored the urgent need for novel antiviral strategies. One of the primary targets of interest is the SARS-CoV-2 main protease (Mpro), which plays a crucial role in viral replication. Building on our prior work involving machine learning (ML)-based virtual screening for potential Mpro inhibitors, we sought to experimentally validate top-ranked candidates. Microscale thermophoresis (MST) was used to assess the binding affinity, leading to the identification of three promising hits from a library of 180 compounds. Notably, one compound demonstrated high-affinity binding to SARS-CoV-2 Mpro (K_d = 2.8 ± 0.9 µM). However, enzymatic assays revealed that none of the hit compounds inhibited the acti

SUBMITTER: Fassi EMA 

PROVIDER: S-EPMC12701685 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature