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