Mechanisms of anti-viral compounds against human enterovirus 71 (EV71) 

• Developed a model of the EV71 pentamer with a scaffold and frozen water layer to specifically study the interactions on the external surface; 

• Employed MD simulations to explore the interactions between the EV71 pentamer and the selected anti-EV71 compounds; 

• Investigated the vibration modes of the entire EV71 capsid through normal mode analysis using the anisotropic network model.

Outcomes and impact: 

•  Identified the presence of stable-bound urea within the protein-protein interface, leading to reduced stability of the viral capsid structure; 

• Discovered that glutaraldehyde and paraformaldehyde are located proximal to specific lysine residues, facilitating the formation of crosslinks; 

• Observed enhanced flexibility in the two-fold axis of the formaldehyde-treated EV71 capsid, which potentially impacts the genome release process; 

• Provided a molecular perspective on two significant mechanisms of action for anti-EV71 compounds: hydrogen-bond competition and the formation of cross-linked structures.

Shi, H., Maupin, M., Fox, S.†, & Yeo, J.† (2024, in preparation). Antiviral effects and molecular mechanisms of different types of compounds against EV71.