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Skip to 0 minutes and 12 secondsIn this short video, we're going to look at drugs which are used to treat influenza. When we're ill with what we think is the flu, we tend to do quite a bit of self-medication. And there's an enormous industry out here that tries to sell us cold and flu remedies. However, these remedies don't really cure the disease. They don't attack the influenza virus or do much at all to alter the course of the infection. They simply make us feel a little better. So this is what we call symptomatic therapy. You might be convinced that your attack of flu has been cured, but if so, that's actually more the result of your own immune system than any medication.

Skip to 0 minutes and 51 secondsI should stress at this point that I'm not dismissing symptomatic therapy as pointless. In some diseases, it's absolutely crucial. For instance in diarrhoeal diseases such as rotavirus or cholera, stopping the diarrhoea can prevent dehydration and actually save the patient's life. So there is definitely a role for symptomatic therapy in many diseases, but in influenza, it's a little less crucial. The exception might be in cases where the patient has worsened to the point of developing pneumonia. In which case, drugs to widen the airways and assist breathing would almost certainly be administered along with an oxygen supply. But let's draw back from this extreme case and think about how you might treat some of the more typical symptoms.

Skip to 1 minute and 39 secondsThe most obvious of these is fever. There are some fairly effective fever reducing medications available, including of course aspirin which has been around since the beginning of the 20th century and which has its origins in folk remedies involving things like boiled willow bark. These medicines are referred to collectively as anti-pyretics and they work in various different ways. One disadvantage of most of them however, is that in high doses they're poisonous. It's therefore really important not to take more than is recommended on the bottle and not to mix remedies. For instance, a general cold and flu remedy sold in a sachet may contain an anti-pyretic as one of several ingredients.

Skip to 2 minutes and 21 secondsSo you ought not to supplement it with individual anti-pyretic remedies taken in tablet form. There's also a more general and more controversial argument that fever is beneficial to the individual suffering from flu and that we therefore ought not to use anti-pyretics at all. According to that view, fever should be seen not as a symptom of infectious disease but rather as one of our natural responses to it produced by the innate immune system. Nevertheless, if a fever is completely out of control, it is dangerous. The general threshold for serious medical intervention is at 41 degrees Celsius. Many people however, find fever so unpleasant that they want to stop it completely.

Skip to 3 minutes and 5 secondsIn which case, anti-pyretics-- as long as you don't take too many-- are very effective. Another common ingredient in compound anti-cold and flu remedies is a stimulant such as ephedrine. This is a relative of the illegal drug amphetamine and is also a banned substance for athletes, many of whom have inadvertently found themselves in trouble for consuming anti-cold remedies before the competition. It also acts as a decongestant relieving blocked airways. The third ingredient in the cocktail is usually a painkiller which can help ease your aching head and bones. Sometimes, the pain killer is also an anti-pyretic. One further medicine is often used-- although it's rarely found as a component of cold and flu mixture remedies-- is antihistamines.

Skip to 3 minutes and 53 secondsSo just as these stop the sneezing and the running noses that are caused by hayfever, they can also relieve the same symptoms in a flu infection. So this is not an exhaustive list of the remedies people try for the flu, but it does cover the main symptomatic categories. A more direct attack on the influenza virus is provided by compounds that target viral proteins. These aren't symptomatic treatments, but aim to be directly curative. The first category are the neuraminidase inhibitors. Neuraminidase, along with haemagglutinin, is one of the proteins that defines a subtype of a flu strain for example H1N1, H3N2 and so on. Commercial examples of neuraminidase inhibitors include Zanamivir, marketed as Relenza, and Oseltamivir, marketed as Tamiflu.

Skip to 4 minutes and 43 secondsOpinion on their effectiveness has been rather divided and some resistant strains of flu have emerged. Resistance is always a problem with drugs that directly target parts of a virus since viruses evolve so quickly. Other drugs target the matrix protein-- Amantadine, marketed as Symmetrel, and Rimantadine marketed as Flumadine. Again, since their use began, some strains of resistant flu have started to appear. Umifenovir or Arbidol, is used in Russia only and is thought to work by preventing viral entry to the cell. Although, its exact molecular target is still undetermined. Another drug with a restricted global licencing is Favipiravir, or Avigan, which is licenced in Japan. Avigan inhibits the viral RNA polymerase and may have a broader spectrum than just influenza.

Skip to 5 minutes and 34 secondsIn the 2014 Ebola virus outbreak in West Africa, it was one of the experimental drugs tested with some evidence of efficacy against Ebola virus. As well as the drugs that have been marketed in various places, we have some experimental compounds. The problems with resistance that have begun to emerge with matrix protein or neuraminidase antagonists mean it's very important that we continue to look for new avenues of treatment. Thiazolides are a class of new drugs of this sort and attack the viral haemagglutinin. Although this is a novel target, we would expect resistance to build after a while, as it has done for the other drugs. One way around this to target host proteins-- in other words proteins in our own cells.

Skip to 6 minutes and 18 secondsThe rationale for this is that it will make it much harder for resistance to evolve. For instance, a Verdinexor targets exportin, a cellular protein that's hijacked by the flu virus as part of its life cycle. Without a host exporting function, the virus can't replicate. When targeting host proteins in this way, we always run the risk of toxicity. But so far, Verdinexor has not shown any toxicity in mice. So to recap, we have firstly some older direct influenza protein targeting drugs that are already starting to produce resistant strains. And secondly, we have some newer drugs that target other proteins but which we expect will eventually suffer the same problems.

Skip to 7 minutes and 3 secondsAnd in a third category, we have some compounds that target our own proteins that are hijacked by the flu which have better prospects perhaps of lasting longer before resistance sets in, but which are potentially more toxic. And fourthly, we have a handful of other less well characterised things such as Arbidol. Despite the problems associated with influenza drug development-- which are general problems in all antiviral research and not necessarily specific to the flu-- it's vitally important that we continue to try because although vaccination and symptomatic treatment are probably better strategies for dealing with seasonal flu, the next pandemic will almost certainly render our vaccines useless. So we'll be back to square one.

Skip to 7 minutes and 49 secondsAnd while the immunologists will be working around the clock to produce a vaccine to the new pandemic strain whatever it is, the only other thing we might have to prevent global catastrophe will be our armoury of anti-influenza drugs.

Antivirals

In the last sections, we saw how diagnostic techniques are performed. Kate took a nasal swab from Derek, which can be used to diagnose the presence of flu virus in the nasal passages using PCR (not demonstrated), and then Martin took a blood sample from Derek, which could be used to detect viral antigen in Derek’s blood, using Western Blotting, or the presence of anti-influenza antibodies in Derek’s blood, using ELISA. Western Blotting and ELISA were demonstrated by Katharina and Lisa in the previous video.

In this video, we’ll assume that a positive diagnosis has been obtained, and move on to cover the range of drug treatment options for an influenza infection.

Some of these are very tried and trusted, and can be bought over the counter in a pharmacy. Others are rather more experimental and only available in extreme cases. The over-the-counter remedies tend to be symptomatic therapies, whereas the new treatments tend to attack the virus directly.

As with antibiotics, anti-virals can become useless when resistance arises. We’ll also be looking at some drugs designed to avoid these problems, and finally considering why, when we have vaccination and other methods for reducing transmission, drug discovery is still a vital activity in the flight against influenza.

As you watch the video, think about how the action of anti-virals is similar or dissimilar to the action of the immune system. Also think about the other drugs that aren’t actually anti-viral - the symptomatic therapies. Based on your understanding of the immune system, think about how they modulate the immune system’s actions.

Some links to further reading can be found below.

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This video is from the free online course:

Influenza: How the Flu Spreads and Evolves

Lancaster University

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