Antiviral therapeutic approaches for human rhinovirus infections

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

A further therapeutic strategy may be targeting of host factors that have been identified as important in the context of RV replication. For example, both oxysterol binding protein (OSBP) and phosphatidylinositol 4-kinase III β (PI4KB), have been identified as host proteins involved in picornavirus replication [133, 134, 135] , and studies focusing upon chemical inhibition of PI4KB with a panel of aminothiazoles have demonstrated potent inhibition of RV [136] . Equally, novel enviroxime-like compounds as well as other compounds such as itraconozole (mentioned above) which can target OSBP have also shown promise in inhibiting viral replication [61, 62, 134, 137] . Furthermore, as both PI4KB and OSBP can act as substrates for protein kinase D (PKD), recent studies have identified PKD as a key molecule in RV replication and have demonstrated that PKD inhibition can profoundly affect RV replication at an early stage [138] . Interestingly, the lipid-modifying enzyme PLA2G16 has recently been described as playing a role in picornavirus replication through enhanced viral protein synthesis [139] . Of note, a very recent study reported that a novel compound, termed IMP-1088, showed potent inhibitory activity towards multiple strains of RV at nanomolar concentrations. This particular compound blocked viral replication by targeting the host cell N-myristoyltransferases NMT1 and NMT2, which are required for the assembly of the viral capsid [140] . Thus, therapeutic options targeting inhibition or functional modulation of these enzymes, or others involved in viral protein synthesis, may be of value.