Rhinoviruses and enteroviruses are leading causes of respiratory infections. To evaluate genotypic diversity and identify forces shaping picornavirus evolution, we screened persons with respiratory illnesses by using rhinovirus-specific or generic real-time PCR assays. We then sequenced the 5′ untranslated region, capsid protein VP1, and protease precursor 3CD regions of virus-positive samples. Subsequent phylogenetic analysis identified the large genotypic diversity of rhinoviruses circulating in humans. We identified and completed the genome sequence of a new enterovirus genotype associated with respiratory symptoms and acute otitis media, confirming the close relationship between rhinoviruses and enteroviruses and the need to detect both viruses in respiratory specimens. Finally, we identified recombinants among circulating rhinoviruses and mapped their recombination sites, thereby demonstrating that rhinoviruses can recombine in their natural host. This study clarifies the diversity and explains the reasons for evolution of these viruses.
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Pleconaril (Picovir, VP-63843, Win-63843) is a broad spectrum antipicornaviral agent that inhibits rhinovirus replication by interaction with the VP1 protein; inhibits EV-D68 with EC50 of 430 nM; shows active against viruses in the Picornaviridae family, including Enterovirus and Rhinovirus.
Rupintrivir (AG-7088, AG7088) is a potent, irreversible inhibitor of human rhinovirus 3C protease, inhibits the replication of all HRV serotypes with EC50 of 23 nM and EC90 of 82 nM; potently and irreversibly inhibits HRV 3C protease with an inactivation rate constant (kobs/[I]) of 1,470,000 ± 440,000 M-1 s-1 for HRV 14; also potently inhibits related picornaviruses including coxsackieviruses A21 and B3, enterovirus 70, and echovirus 11.
Vapendavir (BTA798) is a novel potent enteroviral capsid binder, inhibits EV71 replication of all isolates with mean EC50 of 0.7 uM; efficiently inhibits the in vitro replication of 21 EV71 strains/isolates that are representative of the different genogroups A, B, and C; Vapendavir (BTA798) is currently under clinical study for the treatment of rhinovirus infections.
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