Antiviral therapeutic approaches for human rhinovirus infections

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

In our literature review, we have also identified a number of other small compounds that have been investigated as novel inhibitors of RV over the past four decades. These include the compound 2-(3,4-dichlorophenoxy)-5nitrobenzonitrile (MDL-860) which showed antiviral activity against RV and other viral pathogens [57, 58] . Other studies have identified novel ((biphenyloxy)propyl) isoxazole derivatives as having activity against RV-2 [59] . A very recent report describes a series of benzothiophene derivatives [60] that inhibited the replication of a number of RV serotypes and was proposed to act through viral capsid binding in a similar way to pleconaril. Recently, three novel epidithiodiketopiperazines (KCN-2,2'-epi-19, KCN-19 and KCN-21) were synthesized that displayed activity against RV-87 [33] . Interestingly, the antifungal compound itraconozole has recently been found to have in vitro and in vivo antiviral activity in RV infection [61] . This was potentially due to inhibition of cellular cholesterol trafficking, a process the authors suggest, in accord with another study [62] , is essential for RV replication. This activity was retained when assessing the antiviral activity of itraconozole-loaded microemulsion droplets as carriers for the drug [63] , Indeed, antiviral nanoparticles have been proposed to be excellent candidates for the development of antiviral therapeutics as their activity can extend across a broad range of pathogens [64] , although further investigation on the in vivo effects of different nanoparticle formulations is required, as we have recently shown carbon nanoparticles to be capable of inhibiting the antiviral effects of the human cathelicidin, LL-37, toward RV in vitro [65] .