Key result
The z-LVLQTM-fmk peptide, a pseudosubstrate of the viral 2A protease, significantly reduced human rhinovirus replication in the lungs of infected mice compared to vehicle control.
The LVLQTM peptide acts as a pseudosubstrate of the HRV 2A protease and inhibits viral replication in vitro and in vivo, representing a potential antiviral strategy.
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Provides proof-of-concept for HRV 2A inhibition in mice; leaves open human efficacy and safety.
Human rhinoviruses (HRVs) remain a significant public health problem as they are the major cause of both upper and lower respiratory tract infections. Unfortunately, to date no vaccine or antiviral against these pathogens is available. Here, using a high-throughput yeast two-hybrid screening, we identified a 6-amino-acid hit peptide, LVLQTM, which acted as a pseudosubstrate of the viral 2A cysteine protease (2A(pro)) and inhibited its activity. This peptide was chemically modified with a reactive electrophilic fluoromethylketone group to form a covalent linkage with the nucleophilic active-site thiol of the enzyme. Ex vivo and in vivo experiments showed that thus converted, LVLQTM was a strong inhibitor of HRV replication in both A549 cells and mice. To our knowledge, this is the first report validating a compound against HRV infection in a mouse model.
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Falah et al. (2011) studied Human rhinovirus infection. z-LVLQTM-fmk peptide vs. 1% DMSO or z-FA-fmk control peptide was evaluated on Viral titer (TCID50/ml) in lungs (p=<0.05). The z-LVLQTM-fmk peptide, a pseudosubstrate of the viral 2A protease, significantly reduced human rhinovirus replication in the lungs of infected mice compared to vehicle control.
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