An Insight to COMMON COLD :An Insight to COMMON COLD Rakesh Kumar Majhi rakesh[at]niser[.]ac[.]in School of Biological Sciences NISER, Bhubaneswar


What Is a Common Cold ? :What Is a Common Cold ? A common cold is an illness caused by a virus infection located in the upper respiratory tract. Colds last on average for one week. Mild colds may last only 2 or 3 days while severe colds may last for up to 2 weeks. Signs and symptoms of a common cold may include: • Runny or stuffy nose • Itchy or sore throat • Cough • Congestion • Slight body aches or a mild headache • Sneezing • Watery eyes • Low-grade fever (up to 1020 F)


What causes Common Cold ? :What causes Common Cold ? More than 200 different types of viruses cause common cold. The rhinovirus is the most common culprit, and it's highly contagious. Because so many different viruses can cause common cold, & new cold viruses constantly develop i.e. the viral strains are not stable, the body never builds resistance against all of them. For this reason , colds are a frequent & recurring problem.


WHAT CAUSES COMMON COLD SYMPTOMS ? :WHAT CAUSES COMMON COLD SYMPTOMS ? Cold symptoms are due mainly to the body's response to the infection. When a nasal cell is infected by a cold virus, the body responds by activating parts of the immune system and some nervous system reflexes. The immune system contains a variety of natural substances called inflammatory mediators. Inflammatory mediators help to protect the body from infection and other harmful events. Some inflammatory mediators are released when nasal cells are infected by a cold virus.


Slide 5:When activated by a cold virus infection, inflammatory mediators cause dilatation and leakage of blood vessels and mucus gland secretion. Inflammatory mediators also activate sneeze and cough reflexes and stimulate pain nerve fibers. These events are what lead to the symptoms of a cold. The inflammatory mediators include histamine, kinins, interleukins, and the prostaglandins. The individual symptoms of a cold are caused by the action of particular inflammatory mediators, although there is some overlapping. Twenty-five percent of people who acquire cold virus infection do not develop symptoms.


Does it have anything to do with exposure to cold weather ? :Does it have anything to do with exposure to cold weather ?


What is the difference between Common Cold & Flu (Influenza) ? :What is the difference between Common Cold & Flu (Influenza) ?


# IS IT COLD OR ALLERGY ? :# IS IT COLD OR ALLERGY ?


When should a Physician be consulted ? :When should a Physician be consulted ? • Fever of 1020 F or higher • High fever accompanied by aches and fatigue • Fever accompanied by sweating, chills and a cough with colored phlegm • Symptoms that get worse instead of better or last more than about 10 days


How to prevent Common Cold? :How to prevent Common Cold? Wash your hands Scrub your stuff Use tissues Don’t share Steer clear of colds Consider the alternatives : Vitamin C, Echinacea and Zinc Drink lots of fluids: Water, juice, tea and warm soup Try chicken soup: anti-inflammatory & relieves congestion Get some rest


Common Cold Myths: :Common Cold Myths: The Weather Antibiotics Echinacea Vitamin C


Over The Counter Drugs :Over The Counter Drugs 1.Pharyngeal Demulcents 2.Expectorants (Mucokinetics)? 3.Antitussives (Cough centre suppressants)? 4.Pain Relievers


1.Pharyngeal Demulcents :1.Pharyngeal Demulcents Sooth the throat Reduce afferent impulses from the inflamed / irritated pharyngeal mucosa Thus provide symptomatic relief in dry cough arising from throat.


2. Expectorants (Mucokinetics): :2. Expectorants (Mucokinetics): are drugs that increase bronchial secretion or reduce its viscosity thus facilitating its removal by coughing i.e. make coughs more productive . Therefore they are also referred to as decongestants . If excessive mucus is permitted to settle in the lungs, pneumonia can develop Expectorants are of two types:


Slide 17:1) Bronchial secretion enhancers: Sodium & Potassium Citrates increase bronchial secretion by salt action. They irritate airway mucosa & hence induce coughing. Plant products such as Guaiphenesin, vasaka, tolu balsam are used nowadays. However adequate amount of Hydration is required to dilute mucus. 2) Mucolytics: Bromhexine, a derivative of Adhatoda vasika , & Ambroxol, a metabolite of bromhexine, depolymerise mucopolysaccharides directly as well as by liberating lysosomal enzymes . These are especially useful in removing mucus plugs.


3. Antitussives: :3. Antitussives: These act on CNS to raise the threshold of cough centre or act peripherally in the respiratory tract to reduce tussal impulses, or act in both the ways. Since they act to control rather eliminate cough, antitussives should be used only for dry unproductive cough especially when cough is unduly tiring, disturbs sleep or is harmful Antitussives are of 4 types:


Opioids : :Opioids : Codeine, an opium alkaloid, suppresses cough for about 6 hours, & is expressed through its action on opioid receptors in the brain. Asthmatics & patients with diminished respiratory reserve should avoid it as it has side effects similar to that of morphine.


Non-Opioids: :Non-Opioids: Noscapine, an other opium alkaloid, depresses cough but doesn't have narcotic, analgesic, or addictive properties. However, since it can release antihistamines that cause bronchial constriction, asthmatics are not advised to use it. Dextromethorphan ,a synthetic d-isomer derivative of codeine, is equally well as it doesn't express through opioid receptors & its effect lasts for ~ 6hrs. It soothes minor throat & bronchial irritations. Benzonatates: anesthetize stretch receptors located in the respiratory passages & in lungs, reducing the cough reflex at its source.


Antihistamines: :Antihistamines: They accord relief due to their sedative & anticholinergic action, but lack selectivity for the cough centre. Though they don't have antitussive action, they have been conventionally added to this category. E.g. Chlorpheniramine, Diphenhydramine, Promethazine (all 1st generation anti-histamines). 2nd generation anti-histamines are ineffective.


Bronchodilators: :Bronchodilators: Give relief incase of bronchospasm which induces or aggravates cough & broncho-constriction. They improve the effectiveness of cough in clearing secretions by increasing surface velocity of airflow during cough.


4. Pain Relievers :4. Pain Relievers Many people take pain relievers for headache, fever, or minor aches. Some examples of pain relievers used as common cold medicine include:   Aspirin Acetaminophen (Tylenol®) Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil®, Motrin®).


Vicks VapoRub :Vicks VapoRub Active Ingredients (Purpose) : Camphor 4.8%(Cough suppressant and topical analgesic)? Eucalyptus oil 1.2%(Cough suppressant)? Menthol 2.6%(Cough suppressant and topical analgesic)?


Benadryl :Benadryl Diphenhydramine (antihistamine)? Ammonium Chloride Sodium Citrate (Bronchial secretion enhancers)? Menthol Ethanol (95%)?


Dilosyn - Expectorant :Dilosyn - Expectorant Methdiazine hydrochloride Ammonium Chloride Sodium Citrate


Vicks Cough & Cold- Antitussive :Vicks Cough & Cold- Antitussive Acetaminophen (Pain reliever / Fever reducer)? Chloropeniramine maleate (Antihistamine)? Dextromethorphan (Cough suppressant)?


Vicks Chesty Cough - Bronchial Secretion Enhancers :Vicks Chesty Cough - Bronchial Secretion Enhancers Guaifenesin (Expectorant)? Dextromethorphan (Cough suppressant)?


Viruses responsible for Common Cold : :Viruses responsible for Common Cold : Rhinoviruses Coronaviruses Adenoviruses Orthomyxoviruses (including influenza A and B viruses, which cause flu) Paramyxoviruses (including several parainfluenza viruses) Respiratory syncytial virus Enteroviruses


# What are HRVs? :# What are HRVs? ss RNA viruses Belong to Picornaviridae family Genome size : 7000 bases. from the Greek word rhin, meaning "nose"


# What’s the exciting news? :# What’s the exciting news? A group of scientists have recently claimed to have sequenced the complete genomes of all catalogued HRVs along with 10 new field samples. Contradictory to previous research, the team found evidence that HRVs can recombine. Research established that HRV A, HRV B, HRV C are distinct serotypes, with each containing a few to many small sub groups.


Slide 32:Evidences suggest that a sub group within HRV A may itself be another species HRV-D. It was found that the spectrum of Rhinoviruses is probably much larger than what was earlier realized. # Will there be an endless number of groups? Possibly NO The new field isolates tested fit nicely into the phylogenetic tree & even some showed more closeness to others.


# What's Next ? :# What's Next ? Ligget & his team plan to sequence 1,000 additional HRV field isolates collected from across the U.S. # Why take this trouble ? With the genomes & the phylogenetic tree , it might be possible to prepare new drugs against specific HRV sub-groups.


# How does the virus enter the cell ? :# How does the virus enter the cell ? 1st step is the attachment of the virus to a receptor on the host cell. Internalization is then followed by un-coating of the Capsid. # How was it established ? Rossmann & his group used cryoelectron microscopic study to establish complex formation between HRV-16 & its intracellular adhesion molecule ICAM-1


# What is HRV-16 ? :# What is HRV-16 ? Icosahedral geometry 60 copies of 3 distinct Outer Coat Sub-units : VP-1, VP-2, VP-3 60 copies of an internal peptide VP-4 RNA Outer surfaces of VP-1 & VP-3 join to form grooves to which ICAM-1 can attach. VP-1 is the most external viral capsid protein. VP-4 is the most internal viral capsid protein.


# What is ICAM-1 ?* Mediates adhesion between Endothelial cells & leukocytes (after injury/stress)* Catalyzes Viral Uncoating :# What is ICAM-1 ?* Mediates adhesion between Endothelial cells & leukocytes (after injury/stress)* Catalyzes Viral Uncoating Extra cellular part consists of 5 Domains linked end to end. 1st Domain (most distal to membrane) acts as Viral Receptor. 1st Domain is shaped like a hand with: A Folded Thumb [to which leukocytes bind] 3 Finger-like projections [binding site for HRV]


# Why are these factors important ? :# Why are these factors important ? Analysis of Receptor-Virus interactions (by Electron Microscopy & Model building from high resolution stuctures of the components) would provide Rational Directions for Anti-Rhinovial drug designing. Such a drug should : Block ICAM-1’s viral binding function Without blocking Leukocyte binding.


# Can such a drug prove a panacea for all colds ? :# Can such a drug prove a panacea for all colds ? NO ! HRVs are responsible only for 40-50 % of the Common Cold. The rest are caused by Different Viruses that have different modes of infection. # Is there any existing antiviral agent ? An Antiviral agent WIN 52084 binds to VP-4 Causes local conformational changes in the Receptor Binding Pockets. Stabilizes Viral Capsid against Enzymatic Degradation


HRV and WIN 52084 :HRV and WIN 52084 A: WIN 52084 (purple) bound to VP1 (blue) in HRV B: WIN 52084 structure C: VP1 (blue)/VP3 (red) with WIN 52084 (not shown)? WIN 52084 is a hydrophobic compound that binds to a pocket within VP1 and inhibits the HRV uncoating (RNA-injection) mechanism


# An Interesting Fact !! :# An Interesting Fact !! A team of scintists at Purdue University have found that Man & Chimpanzee are the only species to get Common Cold. # What does this imply ? There is a distinct difference in ICAM-1’s finger-like projections in these Two species & other animals. # Does this Suggest something ????


# Is the Virus alone responsible for Cold symptoms ? :# Is the Virus alone responsible for Cold symptoms ? HRV’s ability to manipulate our genes is an important factor. HRV hijacks many of our Genes Causes an Overblown Immune Response This ends up with our nose being overblown. ** EXPERIMENT **


References: :References: K D Tripathi, Essentials of Medical Pharmacology 6th ed., Jaypee Publications-2008. Dennis Watt, The Common Cold: a review of the literature, European Journal of Internal Medicine 15 (2004), p79-88. www.genomeweb.com/common cold www.emedtv.com/common cold www.nsaid.nih.gov.in www.vicks.com


Acknowledgements: :Acknowledgements: Dr. Anita Roy – for giving me the freedom to choose a topic of my interest & reviewing the presentation a number of times. Prof. T.N. Naik- for providing me the necessary articles regarding Common Cold viruses. My Friends at NISER who have helped me preparing the presentation.


THANK YOU :THANK YOU DON’T BE FOOLED BY THOSE VIRUSES They are all around you !