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Order Picornavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The x-ray crystal structure of human rhinovirus 14 (HRV14), a member of the Rhinovirus B species and the causative agent of common cold, was resolved to 3.0 Å by Rossmann et al. (1985). Together with the previously described poliovirus virions, they were the first structurally resolved representatives of the great Picornaviridae family. Both the tertiary fold of the VP1, VP2, and VP3 polypeptide chains and their pT = 3 quaternary organization within the HRV14 capsid were very similar to the earlier resolved T = 3 structures of the two RNA plant viruses, namely tomato bushy stunt virus (TBSV) of the Tolivirales order described in Chapter 24 and southern bean mosaic virus (SBMV) of the Sobelivirales order (Chapter 28). The β-barrels in HRV14, like those in SBMV, were wedge-shaped, with the thin end pointing toward the 5- or 3-fold (quasi-6-fold) axes (Rossmann et al. 1985). Furthermore, Edward Arnold and Michael G. Rossmann (1990) refined the structure and identified immunogenic regions, as well as the hydrophobic pocket in VP1, which was the locus of binding for the so-called WIN agents, discovered initially by the Sterling-Winthrop Research Institute and used against HRV.
Determination of Antiviral Activity
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Only nonhuman primates (chimpanzee and gibbon ape) are susceptible to human rhinovirus infection, with the infection manifested as shedding of the virus in the pharynx and by seroconversion [122,123]. A similar infection can be induced in vervet monkeys by an equine rhinovirus [124]. Such animal models, although cumbersome and expensive, have been used for successful antiviral studies [125,126], although follow-up studies on a significant rhinovirus-inhibitory compound active in the chimpanzee infection model failed to prevent respiratory illness in the clinic [127].
Viral-Induced Asthma and Chronic Obstructive Pulmonary Disease
Published in Sunit K. Singh, Human Respiratory Viral Infections, 2014
With the development of culture-independent, molecular techniques for diagnosing respiratory pathogens, increasingly strong evidence has emerged for a role of human rhinovirus (RV) in the onset of asthma.9,16 Human RV belongs to the picornaviridae family within the genus Enterovirus. A total exceeding 100 different strains of RV have been identified. Subclassification of RV has been advanced, distinguishing at least three genetically defined groups, A, B, and C. RV can be further subgrouped depending on their host receptors: intercellular adhesion molecule 1 (ICAM-1) for major group RV (about 90% of known RV serotypes) and low-density lipoprotein receptor (LDL-R) for minor group viruses.20 In an 11-year prospective follow-up study, Hyvärinen MK et al.21 demonstrated that severe RV-induced wheezing in early childhood was associated with asthma in about 40% of children entering teen age; the corresponding association with RSV infections was 20% in their cohort. Other investigators have confirmed such a predominance of RV over RSV. It is not known which RV strains are the most pathogenic ones conferring the greatest risk for subsequent development of asthma.
Molecular characterisation of emerging pathogens of unexplained infectious disease syndromes
Published in Expert Review of Molecular Diagnostics, 2019
Xin Li, Susanna K. P. Lau, Patrick C. Y. Woo
Molecular tests have been widely used for diagnosis of viral infections and monitoring of treatment response. Well-known examples include the herpesviruses, hepatitis B and hepatitis C viruses, respiratory viruses such as influenza virus, human immunodeficiency virus, human papillomavirus, etc. Direct sequencing of viral genomes from clinical specimens has contributed to the characterization of novel viruses and re-discovery of known viruses causing previously unexplained clinical syndromes. Before the severe acute respiratory syndrome (SARS) pandemic in 2003, only two human coronaviruses (HCoVs) HCoV-229E and HCoV-OC43 were known, mainly causing symptoms of common cold. After the extensive description and research into SARS-CoV after 2003, two more HCoVs, HCoV-NL63 and HCoV-HKU1 were identified by different groups of scientists using the Virus-Discovery-cDNA-AFLP (amplified restriction fragment-length polymorphism), or VIDISCA, and sequencing of the RNA-dependent RNA polymerase (pol) gene, respectively, from the nasopharyngeal aspirate of index patients with respiratory tract infections [50,51]. Similarly, a new genetic clade of human rhinovirus (HRV), HRV-C, was discovered by VP4 gene sequence analysis of HRVs detected by reverse transcription-PCR (RT-PCR) from a collection of nasopharyngeal aspirates [52]. There are many more reports in the literature on successful identification of previously uncharacterized viruses by sequencing methods, and the sequence database is continually expanding.
Enteroviruses and coronaviruses: similarities and therapeutic targets
Published in Expert Opinion on Therapeutic Targets, 2021
Varpu Marjomäki, Kerttu Kalander, Maarit Hellman, Perttu Permi
Several high-throughput screens have provided novel drugs to inhibit 3 C proteases. Kuo et al. [52] performed a high-throughput screening containing 6800 small-molecule-compounds. One candidate inhibited picornaviruses and CoV equally: a compound containing dihydropyrazole ring with three substituents, two phenyl groups and N-butyl-benzimidazolylamino-toluene. Also, analogues of this showed good potency against picornaviruses and coronaviruses. These are competitive inhibitors indicating that they bind to the active site. Several other molecules based on this hit were searched from other libraries and tested. This testing revealed several drugs inhibiting both SARS-CoV, HCov-229, Coxsackievirus B3, enterovirus-A71, and human rhinovirus 14 with low µM concentration.
Status asthmaticus requiring extracorporeal membrane oxygenation associated with rhinovirus infection
Published in Journal of Asthma, 2020
Lauren Greenawald, Abigail Strang, Curtis Froehlich, Aaron Chidekel
Asthma is the most common respiratory disorder of childhood, affecting over 15% of the pediatric population [1]. Approximately 80% of patients are diagnosed by age 5 years, with viral pathogens as the primary trigger for exacerbations [2]. Of these viruses, human rhinovirus (HRV) is a common pathogen that causes respiratory tract infections across all ages. HRV infection occurs in a bimodal distribution in North America with peaks in spring and fall. This virus is known to have an important role in the “September asthma epidemic” when children return to school and increased viral exposure leads to a surge in asthma exacerbations [2].