Coxsackie B4 virus are enteroviruses that belong to the Picornaviridae family. These viruses can be found worldwide. They are positive-sense, single-stranded, non-enveloped RNA viruses with icosahedral geometry. Coxsackieviruses have two groups, A and B, each associated with different diseases. Coxsackievirus group A is known for causing hand-foot-and-mouth diseases while Group B, which contains six serotypes, can cause a varying range of symptoms like gastrointestinal distress myocarditis. Coxsackievirus B4 has a cell tropism for natural killer cells and pancreatic islet cells. Infection can lead to beta cell apoptosis which increases the risk of insulitis. Viral structure and genome Coxsackievirus B4 is one of the six serotypes found in Group B and is a positive sense, single-stranded, non-enveloped RNA virus. Its genome is linear and is 7,293 nucleotides in length with both a 5’ and 3’ untranslated region and encodes its own 3’ poly-A tail. The 5’ untranslated region contains an internal ribosomal entry site (Type I IRES). Covalently bonded to the 5’ UTR is the viral protein VPg which aids in viral entry and replication. 2A and 3C are viral proteinases which aid in the cleavage of the polyprotein encoded for by the genome. 3D is the RNA-dependent RNA polymerase (RdRP). 2B, 2C, and 3A are core viral proteins. The genome also codes for 4 capsid proteins, VP4, VP1, VP2, and VP3 that form an icosahedral capsid for the viral particles that is about 30 nm. VP1-VP3 are responsible for the outer surface of the virion, while VP4 is imbedded within the capsid. Altogether, the polyprotein encoded for by the coxsackievirus genome is almost 2,200 amino acids in length, and is eventually cleaved by the 2A and 3C proteinases as well as by host cell proteinases. As Coxsackievirus B4, and all other members of the picornavirus family, are non-enveloped, they are notably resilient to disinfectants, solvents, low pH levels (i.e. stomach acid), low temperatures, and 70% alcohol. Viral replication Attachment, entry and uncoating The capsid of Coxsackie viruses have a distinguishable depression around the fivefold axis, termed the “canyon.” The canyon is thought to help with viral attachment through the interaction with cell surface molecules. (Riabi, 2014) When VP1 binds to the Coxsackie-Adenovirus receptor (CAR), which can be found on heart muscle cells as well as epithelial and endothelial cells, a conformational change causes the host cell receptors to form a pore in the plasma membrane through which the VPg-linked viral