Nucleic-acid-based antiviral agents against positive single-stranded RNA viruses

Positive single-stranded RNA viruses constitute a broad and prevalent group of pathogens that threaten human health and life worldwide. While effective vaccines have been developed for some, such as poliovirus and hepatitis A, others such as coxsackievirus, severe acute respiratory syndrome coronavirus (SARS-CoV) and West Nile virus have no accredited drug treatments. Antisense technologies, which encompass small interfering RNA, antisense oligonucleotides, ribozymes and their chemically modified analogs, involve small sequence-specific nucleic-acid-based molecules that inhibit viral replication at the level of translation. Many antisense oligomers are proven antiviral agents in vitro. In this review, we provide an overview of the antiviral antisense field, highlighting specific studies of interest over the past several years, using our experience with coxsackievirus B3 as a reference point. Overall, both the challenges and successes of existing antisense therapies for positive single-stranded RNA viruses can be paralleled to those for other virus groups, and vice versa.