Sep 2026· Journal of Medicinal Chemistry· Vol 69 19, pp.
22162-22186
· 0 citations· 38 references
Medicine
TL;DR
A novel type of acylthiourea-based proteolysis-targeting chimeras (PROTACs) to induce targeted protein degradation to induce targeted protein degradation in enteroviruses, showing strong anti-EV71 activity by inhibiting viral replication.
Abstract
Enteroviruses are the primary cause of hand, foot, and mouth disease (HFMD). The absence of broad-spectrum antivirals, due to high serotypic and genetic diversity, greatly hampers effective treatment. In this study, we developed a novel type of acylthiourea-based proteolysis-targeting chimeras (PROTACs) to induce targeted protein degradation. Compound X14 was identified as a potent candidate. X14 showed strong anti-EV71 activity by inhibiting viral replication. It directly binds to the EV71 3D polymerase with higher affinity than ribavirin and causes proteasome-dependent degradation of the 3D protein. X14 demonstrated broad-spectrum activity against representative EV-A, EV-B, EV-C, and EV-D enteroviruses and exhibited superior in vivo efficacy compared to the parent compound. X14 is a PROTAC targeting EV71 3D polymerase, making it a promising antiviral candidate and chemical tool for HFMD.
Enterovirus A71 (EV-A71), belonging to the Picornaviridae family, is the primary causative agent of hand, foot, and mouth disease (HFMD) in children under five years of age, and no specific broad-spectrum antiviral therapy is currently available. Despite having extensive research on the EV-A71 3C protease, another nons...
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