Monoclonal antibodies point to Achilles’ heel in picornavirus capsid

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.When Paris pierced Achille's heel with an arrow, it was not just a lucky shot.It was a process which demanded 10 years to accomplish, the help of a god, and a detailed knowledge of the structural weakness of the enemy.The success stemmed from recognizing the exact position to be used as a target, a fact that was not apparent just by looking at the warrior.Similarly, structural information of a virus weakness cannot be inferred solely from virion architecture but has to be corroborated with other structural clues.Virions are under constant attack either from environmental factors or from the immune system defense of the infected host.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 particularly relevant the study of epitopes on the external surface of the capsid targeted by antibodies.Picornaviruses are small, icosahedral, nonenveloped, positive-sense, single-stranded RNA viruses that form one of the largest and most important viral families.Numerous of its members pose serious health or agricultural threats, causing diseases such as poliomyelitis, hepatitis A, or foot-and-mouth disease.