The Common Cold

About two-thirds of colds are caused by rhinoviruses - members of the picomavirus group (as are the polio viruses), and all of them are RNA-(+)-viruses. These have an icosahedral (20-sided, near-spherical) shape and their protein coat is made from four different proteins with widely differing amino acid compositions. It is not therefore surprising that there are more than 90 serotypes hence, there is little possibility of a useful vaccine, and none of us has much chance of becoming immune to all forms of the common cold. Other viruses that produce the symptoms of a cold include coronaviruses, adenoviruses, coxsackie viruses, orthomyxoviruses, paramyxoviruses, respiratory syncitial viruses, echoviruses and enteroviruses. 

The actual process of infection is not as simple as is usually believed. Most of the serotypes share a common receptor on host cells, which is an intercellular adhesion protein called ICAM-1. This is a transmembrane glycoprotein whose extracellular portion comprises several immunoglobulin domains of the IgG class. It appears that the normal role of ICAM-1 is to allow adhesion between the cell and leucocytes during injury or infection. Unwittingly, the ICAM-1 receptor has been hijacked by rhinoviruses as their receptor. Interestingly, ICAM-1 has other functions, which include sequestration of erythrocytes that have been infected by the malaria parasite Plasmodium falciparum, thus allowing them to avoid the attentions of the host s immune system. 

There is little actual rhinovirus in saliva hence kissing is not a normal route of transmission. The fine spray of virus particles produced in a sneeze is much more effective, especially if this is delivered to the interior of the nose. If the droplets have been deposited onto one s hand, then inserting a contaminated finger into the nose, or wiping an eye with the same finger, can cause spread of infection. Typical intermediary surfaces are doorknobs and 

As with influenza, the brevity of the incubation period and the fact that by the time the first symptoms appear, the virus will already be present in large amounts, means that prophylaxis and treatment are difficult. Add to this the fact that the cold may be due to another type of virus, for example, an adenovirus (a DNA virus) or a respiratory syncitial virus, and the problems appear insuperable. And indeed, at present, no drugs have reached the marketplace. The rhinoviruses are RNA-(+)-viruses and have two principal viral enzymes an RNA polymerase and a protease, but although a number of potential enzyme inhibitory drugs have been evaluated in clinical trials, none has reached the marketplace. 

the treatment for the common cold remains largely palliative rather than curative. Administration of anti-inflammatory agents like aspirin, decongestants like ephedrine, and anti-histamines will relieve many of the symptoms without necessarily reducing the period of infection. The codeinelike drug dextromorphan is also used and this acts upon the A-methyl-D-aspartate (NMDA) receptors in the brain to increase the threshold for cough induction. One new experimental treatment involves the intranasal administration of ICAM-1 fragments to saturate the receptors. 

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In this chapter we will examine the construction principles of spherical viruses, the structures of individual subunits and the host cell binding properties of the surface of one of the picornaviruses, the common cold virus. 

Drugs against the common cold may be designed from the structure of rhinovirus... 

In more recent times, large doses of vitamin C have been claimed to prevent the common cold, cure infertility, delay the onset of symptoms in acquired immunodeficiency syndrome (AIDS), and inhibit the development of gastric and cervical cancers. None of these claims have been backed by medical evidence, however. In the largest study yet done of the effect of vitamin C on the common cojd, a meta-analysis of more than 100 separate trials covering 40,000 people found no difference in the incidence of colds between those who took supplemental vitamin G regularly and those who did not. When taken during a cold, however, vitamin C does appear to decrease the cold s duration by 8%. 

M ore than 200 viruses have been identified as capable of producing disease Acute viruses, such as the common cold, have a rapid onset and quick recovery. Chronic viral infections, such as acquired immunodeficiency syndrome (AIDS), have recurrent episodes of exacerbations (increases in severity of symptoms of the disease) and remissions (periods of partial or complete disappearance of the signs and symptoms). Display 14-1 describes the viruses discussed in this chapter. 

Decongestants are used to treat the congestion associated with rhinitis, hay fever, allergic rhinitis, sinusitis, and the common cold. In addition, they are used in adjunctive therapy of middle ear infections to decrease congestion around the eustachian tube Nasal inhalers may relieve ear block and pressure pain during air travel. Many can be administered orally as well as topically, but topical application is more effective than the oral route. 

Ephedra is used in diet products as an appetite depressant and stimulant, and in sports drinks to mask fatigue. It is also used as a bronchial stimulator, and to relieve symptoms of the common cold. 

Rhinoviruses cause a significant fraction of the common colds suffered by the human population. However, members of the Rhinovirus genus (Picomaviridae family) include 100 different serotypes that infect humans, making a vaccine strategy impractical. Thus, alternative strategies are needed to intervene in these non-life-threatening but inconvenient infections. 

Rhinoviruses Naked icosahedra 30 nm in diameter The common cold viruses there are over 100 antigenioally distinct types, hence the diffiouity in preparing effective vaccines. The virus is shed copiousiy in watery nasai secretions... 

Virus infections such as influenza and the common cold (in reality 300-400 different strains ofrhinovirus) infect epithelial cells ofthe respiratory tract and nasopharynx, respectively. Release ofthe virus, after lysis ofthe host cells, is to the void rather than to subepithelial tissues. The epithelia is further infected resulting in general degeneration ofthe tracts. Such damage predisposes the respiratory tract to infection with opportunistic pathogens such as Neisseria meningitidis and Haemophilus influenzae. 

The intensity of the daily chronic maintenance regimen varies based on patient age, baseline lung function, other organ system involvement, and social factors such as time available for therapy and patient-selected care choices. Generally, with more severe lung disease and multi-organ system involvement, therapies become more complicated and time intensive. Additionally, therapy is intensified when pulmonary symptoms are increased with acute exacerbations or even mild viral upper respiratory illness such as the common cold. The approach to treatment is best described by the organ system affected. 

Rest, fluids, humidified air, and nasal saline are the mainstays of nonpharmacologic therapy for the common cold. Pregnant women experiencing cold symptoms should be advised of these strategies and reminded that cold symptoms typically last only 7 to 10 days. 

Respiratory viruses are by far the most common infectious agents associated with acute bronchitis. The common cold viruses, rhinovirus and coronavirus, and lower respiratory tract pathogens, including influenza virus, adenovirus, and respiratory syncytial virus, account for the majority of cases. Mycoplasma pneumoniae also appears to be a frequent cause of acute bronchitis. Other bacterial causes include Chlamydia pneumoniae and Bordetella pertussis. 

Another potential benefit of UHPLC is its capability of solving the most challenging separation tasks in pharmaceutical analysis. Figure 9.4 shows a UPLC method developed to analyze pharmaceutical formulations used to treat the common cold. Cold products often contain multiple active ingredients to treat different symptoms and can contain decongestants, antihistamines, pain relievers, cough suppressants, expectorants, and numerous excipients of various polarities. The analysis of a total of 20 components was achieved within 10 min. 

After iron, zinc is the second most abundant trace element in the human body an average adult has 3 g of Zn, corresponding to a concentration of about 0.6 mM. Some 95% of zinc is intracellular. It is essential for growth and development in all forms of life, and has been proposed to have beneficial therapeutic and preventative effects on infectious diseases, including a shortening of the length of the common cold in man. 

Fig. 9.13 An icosahedral host, (a) X-ray crystal struture of the rhino-virus, a spherical virus linked to the common cold, (b) a schematic representation of the rhinovirus displaying triangulation.

For example, let us consider the common cold, often thought of as a disease entity of great economic importance because so many people are afflicted. Medical science has been searching for decades, and for the most part in vain, for a treatment for this affliction. Many, many measures have been enthusiastically embraced, one after another, and have then been discarded because they do not work, generally speaking. 

We have used the common cold as an example there are doubtless other examples where the same principle applies and where the recognition of biochemical individuality will make for the avoidance of attempting the impossible and will thus bring improvement to practical therapeutics. 

Human rhinoviruses (HRV) are members of the Picornaviridae family. The HRVs are classified according to their receptor specificity into members of the major and minor groups. The 87 members of the major-group viruses bind to the intracellular adhesion molecule receptor 1 (ICAM-1), whereas the 12 serotypes of the minor group bind to members of the low-density lipoprotein receptor family (LDLR) [42]. Rhinoviruses cause more than a billion cases of the common cold each year and are also associated with asthma exacerbations [43,44]. Statistically, one encounters one to three infections per year on the average [45]. As a result, rhinoviral infections are responsible for 25 million days of missed work in the USA [46]. 

Let s conclude this discussion of life with a short consideration of viruses. Viruses cause all sorts of problems for living organisms. The problems are the consequence of their ability to infect, and ultimately kiU, many types of cells— bacterial, animal, and plant—though each virus is quite specific in terms of the type of cell that it infects. There are many types of viruses. In people, they cause measles, mumps, influenza, AIDS, polio, potentially fatal diarrhea in infants and very young children, herpes, chicken pox, shingles, the common cold, and many other diseases, that may be fatal, serious, and not so serious. In other animals, viruses also cause any number of diseases, as they do in plants. Much effort has been, and continues to be, devoted to the prevention, diagnosis, and treatment of viral diseases. 

The results of clinical trials of Echinacea for the common cold are provided in ... 

Suppose a researcher develops a drug that is intended to cure the common cold. He gives the drug to a volunteer who has just contracted a viral cold. One week later the volunteer no longer has a cold, and the researcher announces to the press that his drug is a success. Comment. Suggest a better experimental design. 

Horses common cold the rhinoviras is responsible for the common cold ... 

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