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Journal of the American Pharmacists... 2004To review the laboratory and clinical evidence of the medicinal value of zinc for the treatment of the common cold. (Review)
Review
OBJECTIVE
To review the laboratory and clinical evidence of the medicinal value of zinc for the treatment of the common cold.
DATA SOURCES
Published articles identified through Medline (1980-2003) using the search terms zinc, rhinovirus, and other pertinent subject headings. Additional sources were identified from the bibliographies of the retrieved articles.
STUDY SELECTION
By the author.
DATA EXTRACTION
By the author.
DATA SYNTHESIS
Human rhinoviruses, by attaching to the nasal epithelium via the intracellular adhesion molecule-1 (ICAM-1) receptor, cause most colds. Ionic zinc, based on its electrical charge, also has an affinity for ICAM-1 receptor sites and may exert an antiviral effect by attaching to the ICAM-1 receptors in the rhinovirus structure and nasal epithelial cells. Clinical tests of zinc for treatment of common colds have been inconsistent, primarily because of study design, blinding, and lozenge contents. Early formulations of lozenges also were unpalatable. In three trials with similar study designs, methodologies, and efficacy assessments, zinc effectively and significantly shortened the duration of the common cold when it was administered within 24 hours of the onset of symptoms. Recent reports of trials with zinc gluconate administered as a nasal gel have supported these findings; in addition, they have shown that treatment with zinc nasal gel is effective in reducing the duration and severity of common cold symptoms in patients with established illness.
CONCLUSION
Clinical trial data support the value of zinc in reducing the duration and severity of symptoms of the common cold when administered within 24 hours of the onset of common cold symptoms. Additional clinical and laboratory evaluations are warranted to further define the role of ionic zinc for the prevention and treatment of the common cold and to elucidate the biochemical mechanisms through which zinc exerts its symptom-relieving effects.
Topics: Chemistry, Pharmaceutical; Common Cold; Gluconates; Humans; Intercellular Adhesion Molecule-1; Randomized Controlled Trials as Topic; Rhinovirus; Treatment Outcome; Zinc Acetate
PubMed: 15496046
DOI: 10.1331/1544-3191.44.5.594.hulisz -
The Journal of Allergy and Clinical... Jun 2021Young children with rhinovirus (RV) infection-particularly bronchiolitis-are at high risk for developing childhood asthma. Emerging evidence suggests clinical...
BACKGROUND
Young children with rhinovirus (RV) infection-particularly bronchiolitis-are at high risk for developing childhood asthma. Emerging evidence suggests clinical heterogeneity within RV bronchiolitis. However, little is known about these biologically distinct subgroups (endotypes) and their relations with asthma risk.
OBJECTIVE
We aimed to identify RV bronchiolitis endotypes and examine their longitudinal relations with asthma risk.
METHODS
As part of a multicenter prospective cohort study of infants (age <12 months) hospitalized for bronchiolitis, we integrated clinical, RV species (RV-A, RV-B, and RV-C), nasopharyngeal microbiome (16S rRNA gene sequencing), cytokine, and metabolome (liquid chromatography tandem mass spectrometry) data collected at hospitalization. We then applied network and clustering approaches to identify bronchiolitis endotypes. We also examined their longitudinal association with risks of developing recurrent wheeze by age 3 years and asthma by age 5 years.
RESULTS
Of 122 infants hospitalized for RV bronchiolitis (median age, 4 months), we identified 4 distinct endotypes-mainly characterized by RV species, microbiome, and type 2 cytokine (T2) response: endotype A, virusmicrobiomeT2; endotype B, virusmicrobiomeT2; endotype C, virusmicrobiomeT2; and endotype D, virusmicrobiomeT2. Compared with endotype A infants, endotype D infants had a significantly higher rate of recurrent wheeze (33% vs 64%; hazard ratio, 2.23; 95% CI, 1.00-4.96; P = .049) and a higher risk for developing asthma (28% vs 59%; odds ratio, 3.74: 95% CI, 1.21-12.6; P = .03).
CONCLUSIONS
Integrated-omics analysis identified biologically meaningful RV bronchiolitis endotypes in infants, such as one characterized by RV-C infection, Moraxella-dominant microbiota, and high T2 cytokine response, at higher risk for developing recurrent wheeze and asthma. This study should facilitate further research toward validating our inferences.
Topics: Age Factors; Asthma; Bronchiolitis; Common Cold; Disease Susceptibility; Humans; Infant; Infant, Newborn; Metabolome; Proteome; Rhinovirus; Risk Assessment; Transcriptome
PubMed: 33197460
DOI: 10.1016/j.jaci.2020.11.002 -
Journal of Clinical Microbiology Nov 2008Increasing recognition of the association of rhinovirus with severe lower respiratory tract illnesses has clarified the need to understand the relationship between... (Comparative Study)
Comparative Study
Increasing recognition of the association of rhinovirus with severe lower respiratory tract illnesses has clarified the need to understand the relationship between specific serotypes of rhinovirus and their clinical consequences. To accomplish this, a specific and sensitive assay to detect and serotype rhinovirus directly from clinical specimens is needed. Traditional methods of serotyping using culture and serum neutralization are time-consuming, limited to certain reference laboratories, and complicated by the existence of over 100 serotypes of human rhinoviruses (HRVs). Accordingly, we have developed a sequence-based assay that targets a 390-bp fragment accounting for approximately two-thirds of the 5' noncoding region (NCR). Our goal was to develop an assay permitting amplification of target sequences directly from clinical specimens and distinction among all 101 prototype strains of rhinoviruses. We determined the sequences of all 101 prototype strains of HRV in this region to enable differentiation of virus genotypes in both viral isolates and clinical specimens. We evaluated this assay in a total of 101 clinical viral isolates and 24 clinical specimens and compared our findings to genotyping results using a different region of the HRV genome (the VP4-VP2 region). Five specimens associated with severe respiratory disease in children did not correlate with any known serotype of rhinovirus and were found to belong to a novel genogroup of rhinovirus, genogroup C. Isolates were also found that corresponded to the genogroup A2 variant identified in New York and Australia and two other novel group A clusters (GAC1 and GAC2).
Topics: 5' Untranslated Regions; Adult; Animals; Cell Line; Child; Cluster Analysis; Humans; Infant; Macaca mulatta; Molecular Sequence Data; Nasopharynx; Nucleic Acid Amplification Techniques; Phylogeny; Picornaviridae Infections; RNA, Viral; Rhinovirus; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid; Trachea
PubMed: 18753359
DOI: 10.1128/JCM.00674-08 -
Journal of Clinical Virology : the... Aug 2008Human rhinoviruses (HRVs) are the most common cause of viral illness worldwide but today, less than half the strains have been sequenced and only a handful examined... (Review)
Review
BACKGROUND
Human rhinoviruses (HRVs) are the most common cause of viral illness worldwide but today, less than half the strains have been sequenced and only a handful examined structurally. This viral super-group, known for decades, has still to face the full force of a molecular biology onslaught. However, newly identified viruses (NIVs) including human metapneumovirus and bocavirus and emergent viruses including SARS-CoV have already been exhaustively scrutinized. The clinical impact of most respiratory NIVs is attributable to one or two major strains but there are 100+ distinct HRVs and, because we have never sought them independently, we must arbitrarily divide the literature's clinical impact findings among them. Early findings from infection studies and use of inefficient detection methods have shaped the way we think of 'common cold' viruses today.
OBJECTIVES
To review past HRV-related studies in order to put recent HRV discoveries into context.
RESULTS
HRV infections result in undue antibiotic prescriptions, sizable healthcare-related expenditure and exacerbation of expiratory wheezing associated with hospital admission.
CONCLUSION
The finding of many divergent and previously unrecognized HRV strains has drawn attention and resources back to the most widespread and frequent infectious agent of humans; providing us the chance to seize the advantage in a decades-long cold war.
Topics: Common Cold; Humans; Rhinovirus
PubMed: 18502684
DOI: 10.1016/j.jcv.2008.04.002 -
Viruses Nov 2021Rhinoviruses (RV), like many other viruses, modulate programmed cell death to their own advantage. The viral protease, 3C has an integral role in the modulation, and we...
Rhinoviruses (RV), like many other viruses, modulate programmed cell death to their own advantage. The viral protease, 3C has an integral role in the modulation, and we have shown that RVA-16 3C protease cleaves Receptor-interacting protein kinase-1 (RIPK1), a key host factor that modulates various cell death and cell survival pathways. In the current study, we have investigated whether this cleavage is conserved across selected RV strains. RIPK1 was cleaved in cells infected with strains representing diversity across phylogenetic groups (A and B) and receptor usage (major and minor groups). The cleavage was abrogated in the presence of the specific 3C protease inhibitor, Rupintrivir. Interestingly, there appears to be involvement of another protease (maybe 2A protease) in RIPK1 cleavage in strains belonging to genotype B. Our data show that 3C protease from diverse RV strains cleaves RIPK1, highlighting the importance of the cleavage to the RV lifecycle.
Topics: 3C Viral Proteases; Antiviral Agents; Apoptosis; HeLa Cells; Host-Pathogen Interactions; Humans; Isoxazoles; Phenylalanine; Picornaviridae Infections; Protease Inhibitors; Pyrrolidinones; Rhinovirus; Valine
PubMed: 34960671
DOI: 10.3390/v13122402 -
Clinical Microbiology and Infection :... Apr 2015Rhinovirus is the main cause of the common cold, which remains the most frequent infection worldwide among humans. Knowledge and understanding of the rhinovirus...
Rhinovirus is the main cause of the common cold, which remains the most frequent infection worldwide among humans. Knowledge and understanding of the rhinovirus transmission route is important to reduce morbidity as only preventive measures are effective. In this study, we investigated the potential of rhinovirus to survive on fingers. Rhinovirus-B14 was deposited on fingers for 30, 60, 90 and 120 min. Survival was defined as the ability of the virus to grow after 7 days, confirmed by immunofluorescence. Rhinovirus survival was not dependent on incubation time on fingers. Droplet disruption had no influence on survival. Survival was frequent with high rhinovirus concentrations, but rare with low-concentration droplets, which corresponded to the usual rhinovirus concentrations in mucus observed in children and adults, respectively. Our study confirms that rhinovirus infectiousness is related to the viral concentration in droplets and suggests that children represent the main transmission source, which occurs only rarely via adults. It confirms also that rhinovirus hand-related transmission is possible and supports hand hygiene as a key prevention measure.
Topics: Adult; Child; Child, Preschool; Fingers; Healthy Volunteers; Humans; Microbial Viability; Rhinovirus; Time Factors
PubMed: 25614158
DOI: 10.1016/j.cmi.2014.12.002 -
Journal of Medical Virology Feb 2018To determine the prevalence of human rhinovirus (HRV) infection in children with acute asthma exacerbations, investigation of HRV viral load and severity of asthma...
To determine the prevalence of human rhinovirus (HRV) infection in children with acute asthma exacerbations, investigation of HRV viral load and severity of asthma exacerbations is also required. Nasopharyngeal aspirates and swabs were collected and assessed for respiratory viruses. HRV-positive samples were sequenced to identify types and determine viral load. Outpatients with asthma exacerbations underwent follow-up evaluations, their swabs were collected and clinical outcomes were recorded at their next clinic visit 4 weeks later. One hundred forty-three inpatients and 131 outpatients, including 88 patients with asthma exacerbations and 43 controls with stable asthma were recruited. HRV-A was mainly detected in September and February (45.5% and 33.3%, respectively), while HRV-C was mainly detected in November and April (70.0% and 55.6%, respectively). HRV-C was the primary type and was primarily found in inpatients with severe asthma exacerbations. HRV-A viral load in the group of inpatients with severe exacerbations was higher than in the mild and moderate groups (P < 0.001 and P = 0.022). The HRV-A viral load of both inpatients and outpatients was higher than that of HRV-C (P < 0.001 and P = 0.036). The main genotypes were HRV-C53 and HRV-A20 among inpatients, and this genotype caused more severe clinical manifestations. HRV persisted for no more than 4 weeks, and their symptoms or signs of disease were well-controlled well. HRV-C was most frequently detected in asthma exacerbations. HRV-A with high viral load led to severe asthma exacerbations.
Topics: Adolescent; Asthma; Child; Child, Preschool; Disease Progression; Female; Follow-Up Studies; Genotype; Humans; Infant; Male; Picornaviridae Infections; Rhinovirus; Viral Load
PubMed: 28500687
DOI: 10.1002/jmv.24850 -
Human Vaccines & Immunotherapeutics Mar 2020Rhinoviruses are ubiquitous human pathogens of the upper respiratory tract and are the major cause of acute exacerbations of asthma and chronic obstructive pulmonary...
Rhinoviruses are ubiquitous human pathogens of the upper respiratory tract and are the major cause of acute exacerbations of asthma and chronic obstructive pulmonary disease. At least 160 antigenically distinct serotypes or strains have been identified and protective immunity is largely serotype specific. Attempts to produce vaccines that induce broad immunity have met with limited success which is due in part to this antigenic diversity and a lack of information regarding the ideal protective immune responses. Recent approaches identifying conserved rhinovirus epitopes and better definitions of the immune correlates of protection have raised hope. Here, these newer findings are outlined and the prospects for such a universal rhinovirus vaccine are discussed.
Topics: Antibodies, Viral; Asthma; Epitopes; Humans; Pulmonary Disease, Chronic Obstructive; Rhinovirus; Viral Vaccines
PubMed: 31464554
DOI: 10.1080/21645515.2019.1661207 -
Medicinal Research Reviews Jan 2011As the major etiological agent of the common cold, human rhinoviruses (HRV) cause millions of lost working and school days annually. Moreover, clinical studies proved an... (Review)
Review
As the major etiological agent of the common cold, human rhinoviruses (HRV) cause millions of lost working and school days annually. Moreover, clinical studies proved an association between harmless upper respiratory tract infections and more severe diseases e.g. sinusitis, asthma, and chronic obstructive pulmonary disease. Both the medicinal and socio-economic impact of HRV infections and the lack of antiviral drugs substantiate the need for intensive antiviral research. A common structural feature of the approximately 100 HRV serotypes is the icosahedrally shaped capsid formed by 60 identical copies of viral capsid proteins VP1-4. The capsid protects the single-stranded, positive sense RNA genome of about 7,400 bases in length. Both structural as well as nonstructural proteins produced during the viral life cycle have been identified as potential targets for blocking viral replication at the step of attachment, entry, uncoating, RNA and protein synthesis by synthetic or natural compounds. Moreover, interferon and phytoceuticals were shown to protect host cells. Most of the known inhibitors of HRV replication were discovered as a result of empirical or semi-empirical screening in cell culture. Structure-activity relationship studies are used for hit optimization and lead structure discovery. The increasing structural insight and molecular understanding of viral proteins on the one hand and the advent of innovative computer-assisted technologies on the other hand have facilitated a rationalized access for the discovery of small chemical entities with antirhinoviral (anti-HRV) activity. This review will (i) summarize existing structural knowledge about HRV, (ii) focus on mechanisms of anti-HRV agents from synthetic and natural origin, and (iii) demonstrate strategies for efficient lead structure discovery.
Topics: Antiviral Agents; Capsid Proteins; Common Cold; Genome, Viral; Humans; RNA, Viral; Rhinovirus; Structure-Activity Relationship; Viral Proteins; Virus Replication
PubMed: 19714577
DOI: 10.1002/med.20176 -
Journal of Virology Jan 2022Rhinoviruses (RVs) cause recurrent infections of the nasal and pulmonary tracts, life-threatening conditions in chronic respiratory illness patients, predisposition of...
Rhinoviruses (RVs) cause recurrent infections of the nasal and pulmonary tracts, life-threatening conditions in chronic respiratory illness patients, predisposition of children to asthmatic exacerbation, and large economic cost. RVs are difficult to treat. They rapidly evolve resistance and are genetically diverse. Here, we provide insight into RV drug resistance mechanisms against chemical compounds neutralizing low pH in endolysosomes. Serial passaging of RV-A16 in the presence of the vacuolar proton ATPase inhibitor bafilomycin A1 (BafA1) or the endolysosomotropic agent ammonium chloride (NHCl) promoted the emergence of resistant virus populations. We found two reproducible point mutations in viral proteins 1 and 3 (VP1 and VP3), A2526G (serine 66 to asparagine [S66N]), and G2274U (cysteine 220 to phenylalanine [C220F]), respectively. Both mutations conferred cross-resistance to BafA1, NHCl, and the protonophore niclosamide, as identified by massive parallel sequencing and reverse genetics, but not the double mutation, which we could not rescue. Both VP1-S66 and VP3-C220 locate at the interprotomeric face, and their mutations increase the sensitivity of virions to low pH, elevated temperature, and soluble intercellular adhesion molecule 1 receptor. These results indicate that the ability of RV to uncoat at low endosomal pH confers virion resistance to extracellular stress. The data endorse endosomal acidification inhibitors as a viable strategy against RVs, especially if inhibitors are directly applied to the airways. Rhinoviruses (RVs) are the predominant agents causing the common cold. Anti-RV drugs and vaccines are not available, largely due to rapid evolutionary adaptation of RVs giving rise to resistant mutants and an immense diversity of antigens in more than 160 different RV types. In this study, we obtained insight into the cell biology of RVs by harnessing the ability of RVs to evolve resistance against host-targeting small chemical compounds neutralizing endosomal pH, an important cue for uncoating of normal RVs. We show that RVs grown in cells treated with inhibitors of endolysosomal acidification evolved capsid mutations yielding reduced virion stability against elevated temperature, low pH, and incubation with recombinant soluble receptor fragments. This fitness cost makes it unlikely that RV mutants adapted to neutral pH become prevalent in nature. The data support the concept of host-directed drug development against respiratory viruses in general, notably at low risk of gain-of-function mutations.
Topics: Antiviral Agents; Capsid; Capsid Proteins; Drug Resistance, Viral; Endosomes; HeLa Cells; Humans; Hydrogen-Ion Concentration; Intercellular Adhesion Molecule-1; Mutation; Protein Conformation; Rhinovirus; Virion; Virus Internalization; Virus Uncoating
PubMed: 34705560
DOI: 10.1128/JVI.01060-21