Why the study?
Enteroviruses cause widespread human diseases with no approved antiviral therapies currently available, making host-directed therapies targeting host factor SETD3 interacting with viral protease 2A an enticing option.
The study reveals the structural basis of the SETD3-2A interaction, showing that mutations in the SET domain of SETD3 disrupt binding and prevent enteroviral infection, providing a framework for host-directed therapeutics.
Summary Enteroviruses cause a number of medically relevant and widespread human diseases with no approved antiviral therapies currently available. Host-directed therapies present an enticing option for this diverse genus of viruses. We have previously identified the actin histidine methyltransferase SETD3 as a critical host factor physically interacting with the viral protease 2A. Here, we report the 3.5 Å cryo-EM structure of SETD3 interacting with coxsackievirus B3 2A at two distinct interfaces, including the substrate-binding surface within the SET domain. Structure-function analysis revealed that mutations of key residues in the SET domain resulted in severely reduced binding to 2A and complete protection from enteroviral infection. Our findings provide insight into the molecular basis of the SETD3-2A interaction and a framework for the rational design of host-directed therapeutics against enteroviruses.
No takes yet. Share an insight, caveat, or question.
Peters et al. (2022) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: