title: Proteases of human rhinovirus: role in infection.
abstract: Human rhinoviruses (HRV) are the major etiological agents of the common cold and asthma exacerbations, with significant worldwide health and economic impact. Although large-scale population vaccination has proved successful in limiting or even eradicating many viruses, the more than 100 distinct serotypes mean that conventional vaccination is not a feasible strategy to combat HRV. An alternative strategy is to target conserved viral proteins such as the HRV proteases, 2A(pro) and 3C(pro), the focus of this review. Necessary for host cell shutoff, virus replication, and pathogenesis, 2A(pro) and 3C(pro) are clearly viable drug targets, and indeed, 3C(pro) has been successfully targeted for treating the common cold in experimental infection. 2A(pro) and 3C(pro) are crucial for virus replication due to their role in polyprotein processing as well as cleavage of key cellular proteins to inhibit cellular transcription and translation. Intriguingly, the action of the HRV proteases also disrupts nucleocytoplasmic trafficking, contributing to HRV cytopathic effects. Improved understanding of the protease-cell interactions should enable new therapeutic approaches to be identified for drug development.
authors.affiliation: Faculty of Education, Science, Technology and Mathematics, Centre for Research in Therapeutic Solutions, University of Canberra, 1 Kirinari Street, Bruce, Canberra, ACT, 2601, Australia.
authors.forename: Lora M
authors.initials: LM
authors.lastname: Jensen
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Walker
authors.forename: David A
authors.initials: DA
authors.lastname: Jans
authors.forename: Reena
authors.initials: R
authors.lastname: Ghildyal
mesh_terms: D000086042:3C Viral Proteases; D021581:Active Transport, Cell Nucleus; D000998:Antiviral Agents / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010649:Phenylalanine / Q000031:analogs & derivatives; D010850:Picornaviridae Infections / Q000378:metabolism / Q000821:virology; D011760:Pyrrolidinones / Q000494:pharmacology; D012229:Rhinovirus / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity*; D014633:Valine / Q000031:analogs & derivatives; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D007555:Isoxazoles; D011760:Pyrrolidinones; D014764:Viral Proteins; D010649:Phenylalanine; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; C057400:picornain 2A, Picornavirus; D014633:Valine; C118874:rupintrivir