Key result
Elastic network model analysis identified four clusters of key residues controlling the uncoating motions of the CVA16 capsid, providing potential target sites for vaccine design.
Why the study?
There are no available antiviral drugs or effective treatments for CVA16, and intrinsic capsid uncoating hinders vaccine development by potentially destroying neutralizing epitopes.
Identification of key residues controlling the uncoating motions of the CVA16 capsid provides potential target sites to prevent uncoating, which is valuable for vaccine design.
May inform capsid stabilization strategies in CVA16 vaccine design; leaves open whether identified residues alter immunogenicity in vivo.
The coxsackievirus A16 (CVA16) is a highly contagious virus that causes the hand, foot, and mouth disease, which seriously threatens the health of children. At present, there are still no available antiviral drugs or effective treatments against the infection of CVA16, and thus it is of great significance to develop anti-CVA16 vaccines. However, the intrinsic uncoating property of the capsid may destroy the neutralizing epitopes and influence its immunogenicity, which hinders the vaccine developments. In the present work, the functional-quantity-based elastic network model analysis method developed by our group was extended to combine with group theory to investigate the uncoating motions of the CVA16 capsid, and then the functionally key residues controlling the uncoating motions were identified by our functional-quantity-based perturbation method. Several motion modes encoded in the topological structure of the capsid were revealed to be responsible for the uncoating of CVA16 particle. These modes predominantly contribute to the fluctuation of the gyration radius of the capsid. Then, by using the perturbation method, four clusters of key sites involved in the uncoating motions were identified, whose perturbations induce significant changes in the fluctuation of the gyration radius. These key residues are mainly located at the 2-fold channels, the quasi 3-fold channels, the bottom of the canyons, and the inter-subunit interfaces around the 3-fold axes. Our studies are helpful for better understanding the uncoating mechanism of the CVA16 capsid and provide potential target sites to prevent the uncoating motions, which is valuable for the vaccine design against CVA16.
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He et al. (2021) studied Coxsackievirus A16 (CVA16) infection. Functional-quantity-based elastic network model analysis was evaluated on Uncoating motions of the CVA16 capsid and identification of key residues. Elastic network model analysis identified four clusters of key residues controlling the uncoating motions of the CVA16 capsid, providing potential target sites for vaccine design.
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