Pharmacological and biological antiviral therapeutics for cardiac coxsackievirus infections.

Abstract

Subtype B coxsackieviruses (CVB) represent the most commonly identified infectious agents associated with acute and chronic myocarditis, with CVB3 being the most common variant. Damage to the heart is induced both directly by virally mediated cell destruction and indirectly due to the immune and autoimmune processes reacting to virus infection. This review addresses antiviral therapeutics for cardiac coxsackievirus infections discovered over the last 25 years. One group represents pharmacologically active low molecular weight substances that inhibit virus uptake by binding to the virus capsid (e.g., pleconaril) or inactivate viral proteins (e.g., NO-metoprolol and ribavirin) or inhibit cellular proteins which are essential for viral replication (e.g., ubiquitination inhibitors). A second important group of substances are interferons. They have antiviral but also immunomodulating activities. The third and most recently discovered group includes biological and cellular therapeutics. Soluble receptor analogues (e.g., sCAR-Fc) bind to the virus capsid and block virus uptake. Small interfering RNAs, short hairpin RNAs and antisense oligonucleotides bind to and led to degradation of the viral RNA genome or cellular RNAs, thereby preventing their translation and viral replication. Most recently mesenchymal stem cell transplantation has been shown to possess antiviral activity in CVB3 infections. Taken together, a number of antiviral therapeutics has been developed for the treatment of myocardial CVB infection in recent years. In addition to low molecular weight inhibitors, biological therapeutics have become promising anti-viral agents.

• Authors: Henry Fechner, Sandra Pinkert, Anja Geisler, Wolfgang Poller, Jens Kurreck
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 16 Issue 10 Pg. 8475-503 (Oct 11 2011) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 21989310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antiviral Agents
• Oligonucleotides, Antisense
• RNA, Small Interfering
• Interferons

Topics

• Animals
• Antiviral Agents (pharmacology, therapeutic use)
• Coxsackievirus Infections (drug therapy, immunology, therapy)
• Enterovirus (drug effects, immunology)
• Humans
• Interferons (pharmacology, therapeutic use)
• Mesenchymal Stem Cell Transplantation
• Mice
• Myocarditis (drug therapy, immunology, virology)
• Oligonucleotides, Antisense (pharmacology, therapeutic use)
• RNA, Small Interfering (pharmacology, therapeutic use)
• Ubiquitination (drug effects)