Abstract
Picornaviruses are small, icosahedral, nonenveloped, positive-sense, single-stranded RNA viruses that form one of the largest and most important viral families. Numerous Picornaviridae members pose serious health or agricultural threats, causing diseases such as poliomyelitis, hepatitis A, or foot-and-mouth disease. The antigenic characterization of picornavirus capsids plays an important role in understanding the mechanism of viral neutralization and the conformational changes associated with genome release, and it can point to regions which can be targeted by small-molecule compounds to be developed as antiviral inhibitors. In a recent study, Cao and colleagues applied this strategy to hepatitis A virus (HAV) and used cryo-electron microscopy (cryo-EM) to characterize a well-conserved antigenic site recognized by several monoclonal antibodies. They further used computational approaches to identify a small-molecule drug with a strong inhibitory effect on cell attachment.
Highlights
Picornaviruses are small, icosahedral, nonenveloped, positive-sense, single-stranded RNA viruses that form one of the largest and most important viral families
Monoclonal antibodies are weapons of high specificity binding to precise epitopes, forcing the virus to mutate surface residues in order to escape recognition
The complicated geometry of invading arms and loops from VP1, VP2, and VP3 together with the reinforcement provided by VP4 at the interior of the capsid generate a stable capsid capable to harbor the densely packed RNA genome. This state cannot be too rigid: either receptor binding and/or changes in pH have to be able to trigger conformational changes facilitating the delivery of the genome to the cellular cytoplasm where the viral replication takes place
Summary
Monoclonal antibodies (mAbs) are weapons of high specificity binding to precise epitopes, forcing the virus to mutate surface residues in order to escape recognition. This process is much more complicated for icosahedral viruses because their capsid proteins fulfill simultaneously multiple roles. They must protect the viral genome, recognize the cellular receptor, assist viral uncoating, and assemble into newly formed virions. This number of constraints makes relevant the study of epitopes on the external surface of the capsid targeted by antibodies.
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