Antiviral therapeutic approaches for human rhinovirus infections

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

The compound rupintrivir, also known as AG7088, is an inhibitor of viral 3C protease, an enzyme that is virally encoded and essential for RV replication. Studies of rupintrivir in the context of RV infection has revealed that it exhibits moderate antiviral activity in vitro against a range of RV serotypes, enterovirus-71 and coxsackievirus [34, 47, 48, 49, 50, 51] . Additionally, it demonstrated efficacy in a Phase II clinical trial of experimental RV infection and was well tolerated by human subjects in multiple human exposures [52, 53] . Interestingly, a recent study has also revealed that analogs of rupintrivir based on proline and azetidine modifications to this compound have also revealed broad spectrum activity against a range of RV serotypes [54] . Of further interest was the observation that rupintrivir also exhibited in vitro activity against newly discovered human RV C strains [55] . Assessment of the potential for RV to evolve resistance to rupintrivir has also been conducted, with selection of novel RV variants in increasing concentrations of the drug displaying minimal to moderate susceptibility reductions [56] . Collectively, it is clear that this compound, and novel analogs, have potential for the development of novel therapeutics for RV, but that further in vivo trials are required.