Antiviral therapeutic approaches for human rhinovirus infections

Casanova, Victor; Sousa, Filipa H; Stevens, Craig; Barlow, Peter G

An effective licensed therapeutic treatment for RV remains elusive, despite several decades of intensive work that has aimed to characterize the activity of a wide range of naturally occurring and synthetic compounds against this infection. The answer to this problem may lie in manipulation of the host cell response with a view to inhibiting RV replication and spread. For example, one recent study that screened 50,000 potential antiviral structures, and subsequently identified and analyzed the compound FA-613 found that it interferes with intracellular pyrimidine synthesis pathways [149] . Furthermore, the addition of FA-613 to virus-infected cells induced the elevated expression of antiviral genes, leading to inhibition of RV, influenza, RSV and coronavirus replication. This is an example of a host-cell focused strategy that could yield promising results in the future. Another way forward could be the use of peptides that are able to act by blocking receptors, such as ICAM-1 and LDL, essential for RV binding and entry. Cathelicidins can inactivate nonenveloped viruses, such as adenovirus, and optimal inhibition of RV replication occurs when the virus is directly exposed to the peptide, suggesting that peptide binding to a component of the capsid is occurring [70, 82] . At present, virtually nothing is known about the determinants for cathelicidin binding to the viral capsid and a full understanding of this will require fine mapping of cathelicidin binding sites and identification of the active peptide region.