SCAR-Fc

Coxsackievirus B3 is a single-stranded RNA enterovirus and a member of the Picornavirdae family. Once the virus penetrates the host's systemic circulation via contaminated water or food, it can travel and infect the heart and cause myocarditis. Myocarditis is an inflammation of the heart, most commonly cause by viral infections. Amongst the viruses capable of causing myocarditis, CVB3 is a common agent identified in inducing cardiac damage. Internalization of the virus into myocytes occurs by binding to coxsackievirus-adenovirus receptors (CAR) located in tight junctions on cell membranes. Once inside the cytoplasm, the virus can use the host's ribosomal machinery to proliferate and replicate progenies for further infection. Extensive cardiac necrosis can occur by day three after infection as incubated viruses lyse myocytes, resulting in severe and rapid cardiac decompensation. With loss of cardiac cells increasing progressively, infected individual will experience abnormalities in left ventricular systolic and diastolic function, as well as electrical conduction defects manifesting as cardiac dysrhythmias. As a result, ejection fraction decreases substantially. ==Mechanism==

A synthetic and soluble form of CAR (sCAR) has been created to prevent viral infection with CVB3. Attaching Fc domain of immunoglobulin IgG1 to sCAR (sCAR-Fc) enhances solubility and extends its half-life. Furthermore, once sCAR-Fc binds the virus, macrophages and other phagocytic immune cells with Fc receptor recognition bind to the sCAR-Fc-viral complex to eliminate the virus. Essentially, sCAR-Fc mimics CAR receptors on cardiac cells, competitively inhibiting viral attachment and entry into myocytes. Decreased lesions in cardiac tissues, reduced cell necrosis, and diminished inflammatory responses are observed in sCAR-Fc treated cells (CITE). This suggests protective effects against myocardial damage by CVB3. Conformational changes in a viral particle (A-particle) with sCAR-Fc-virus binding causing the loss of the virus’ internal capsid protein, VP4. ==Administration==

Administration of sCAR-Fc beyond three days after initial exposure to the virus does not have any beneficial effects as cardiac damage is too severe. As such, the use of sCAR-Fc is currently limited to prophylactic treatments. ==References==