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Problems and prospects of developing effective therapy for common cold viruses.

No effective treatment for common colds has yet been developed. Combination antiviral and anti-inflammatory therapies are the best hope for intervention after the onset of symptoms. Prophylaxis, especially in the form of vaccination, would have a major impact in disease prevention. These approaches offer new avenues for treating populations at risk and are of particular significance to those with asthma or chronic bronchitis.

Adrenal Cortex Hormones↗

Analysis of common cold virus (human rhinovirus serotype 2) by capillary zone electrophoresis: the problem of peak identification.

Different preparations of human rhinovirus serotype 2 (HRV2), a common cold virus, were analyzed by capillary zone electrophoresis (CZE) in untreated fused-silica capillaries using borate buffer (100 mmol/L, pH 8.3) and sodium dodecyl sulfate (10 mmol/L) as additive to prevent wall adsorption. The electropherograms showed one major peak at 205- and 254-nm detection wavelengths. The identity of the peak as originating from native virus was confirmed by several indirect methods. Heating to 56 degrees C is known to lead to release of the genomic RNA from the viral capsid; this treatment resulted in the disappearance of the major peak and the emergence of a new predominant peak that was identified as RNA by enzymatic digestion. As expected, RNase treatment of the unheated sample remained without effect as the viral genome is inaccessible in the native viral shell. A monoclonal, virus-aggregating antibody was used for immunodepletion of native virus; again, the major peak disappeared upon removal of viral aggregates by centrifugation prior to CZE analysis. In combination, these results allowed for the unambiguous identification of the main peak as native HRV2 and of the minor peaks as contaminants present in various amounts in the different viral preparations. It is demonstrated that CZE allows for an extremely easy and rapid assessment of conformational state and purity of virions in a given viral preparation.

Electrolytes↗

Spectrum of clinical illness in hospitalized patients with "common cold" virus infections.

The viruses associated most frequently with the "common cold" are rhinoviruses and coronaviruses. The first prospective cohort study to determine the prevalence of rhinovirus and coronavirus infections in patients of all ages hospitalized for acute respiratory illnesses is described. Hospital admissions for acute respiratory illnesses were identified, and cell culture for rhinovirus and serologic assays on paired sera for coronaviruses 229E and OC43 were performed. A total of 61 infections with rhinoviruses and coronaviruses were identified from 1198 respiratory illnesses (5.1%); in addition, 9 additional infections associated with >/=1 other respiratory viruses were identified. Of those infected with only rhinovirus or coronavirus, underlying cardiopulmonary diseases were present in 35% of the patients aged <5 years, in 93% aged between 5 and 35 years, and in 73% aged >35 years. The predominant clinical syndromes varied by age: pneumonia and bronchiolitis in children aged <5 years; exacerbations of asthma in older children and young adults; and pneumonia and exacerbations of chronic obstructive pulmonary disease and congestive heart failure in older adults. Therefore, rhinovirus and coronavirus infections in hospitalized patients were associated with lower respiratory tract illnesses in all age groups.

Adolescent↗

Antiviral agent blocks breathing of the common cold virus.

A dynamic capsid is critical to the events that shape the viral life cycle; events such as cell attachment, cell entry, and nucleic acid release demand a highly mobile viral surface. Protein mass mapping of the common cold virus, human rhinovirus 14 (HRV14), revealed both viral structural dynamics and the inhibition of such dynamics with an antiviral agent, WIN 52084. Viral capsid digestion fragments resulting from proteolytic time-course experiments provided structural information in good agreement with the HRV14 three-dimensional crystal structure. As expected, initial digestion fragments included peptides from the capsid protein VP1. This observation was expected because VP1 is the most external viral protein. Initial digestion fragments also included peptides belonging to VP4, the most internal capsid protein. The mass spectral results together with x-ray crystallography data provide information consistent with a "breathing" model of the viral capsid. Whereas the crystal structure of HRV14 shows VP4 to be the most internal capsid protein, mass spectral results show VP4 fragments to be among the first digestion fragments observed. Taken together this information demonstrates that VP4 is transiently exposed to the viral surface via viral breathing. Comparative digests of HRV14 in the presence and absence of WIN 52084 revealed a dramatic inhibition of digestion. These results indicate that the binding of the antiviral agent not only causes local conformational changes in the drug binding pocket but actually stabilizes the entire viral capsid against enzymatic degradation. Viral capsid mass mapping provides a fast and sensitive method for probing viral structural dynamics as well as providing a means for investigating antiviral drug efficacy.

Antiviral Agents↗