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Uploaded:2020-04-10
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You might have heard that we found a cure for the COVID-19, and that it comes from a drug we've used for centuries. But let's take a breath and look at the facts.

#coronavirus #COVID19

Hosted by: Hank Green

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Sources:

https://link.springer.com/article/10.1007/s12016-010-8243-x#Sec5
https://www.ncbi.nlm.nih.gov/pubmed/9719345
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1529-8019.2007.00131.x
https://www.uptodate.com/contents/antimalarial-drugs-in-the-treatment-of-rheumatic-disease
https://www.ncbi.nlm.nih.gov/books/NBK26871/
https://www.ncbi.nlm.nih.gov/books/NBK215631/
https://www.ncbi.nlm.nih.gov/pubmed/14021822
https://www.ccjm.org/content/85/6/459.full
https://www.ncbi.nlm.nih.gov/books/NBK9953/
https://medlineplus.gov/ency/article/002224.htm
https://www.ncbi.nlm.nih.gov/pubmed/25075736
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294426/
https://www.nature.com/articles/s41421-020-0156-0
https://aac.asm.org/content/53/8/3416
https://www.nature.com/articles/s41422-020-0282-0
https://www.ncbi.nlm.nih.gov/pubmed/32205204
https://www.medrxiv.org/content/10.1101/2020.03.22.20040949v1
https://www.ncbi.nlm.nih.gov/pubmed/29517495
This episode was filmed on April 7th 2020.  If we have more recent episodes on COVID-19 or hydroxychloroquine, we'll include them in the description.
*intro music*
All right, everybody's talking about antimalarials and how they are a promising treatment for COVID-1. Let's make the case. Some people are too excited about this; it's gonna end the pandemic if only the scientists would get out of the way. *somewhat sarcastically*  And some people, on the other hand, are reflexively saying that this  definitely won't work. But science does not work that way, and when initial anecdotes look promising, that's when we investigate further. What these drugs are not, is new.
They have been prescribed for malaria and autoimmune conditions for decades, and those are two very different things.  
But if you take a closer look at the chemistry involved, you can start to understand how these drugs can do so much.  
But that doesn't mean that we know how they work for COVID-19, or even if they do.
There are good reasons to think they might, but like with many things surrounding this illness, there's a lot we need to figure out.  
The two medications making international headlines are hydroxychloroquine and chloroquine.  
That "quine" in their names come from the fact that their chemical structure is similar to quinine- or as some call it, "kwih-nihn" (pronunciation).  
And if you've heard that name before, it's probably because humans have been using it to treat malaria for centuries. 
But quinine shortages during WWII prompted German and US chemists to look for alternatives.  So they turned to chloroquine, quinine's chlorine-toting cousin, which was first synthesized in the 1930s. And since that has some pretty unpleasant side effects, the less-toxic hydroxychloroquine was introduced in the 1950s.
Now, the parasites that cause malaria are very different from the virus that causes COVID-19.  Like, as different as diseases can get form each other, and both might seem totally unrelated to the autoimmune conditions like lupis that these drugs are regularly perscribed for. 
But once you understand what these antimalarials actually do to cells; including their ability to fend off parasites and treat autoimmuntiy, their ability to fight a viral infection actually makes a lot more sense.
Let's start with the parasites, because these drugs were devoloped as antimalarials.  
Dispite the long history, it is not 100% clear exactly how these drugs teat malaria, though we know the big picture; they kill the parasites.  The first reason they cand do that is because of their chemical structure; these compournds cand get all up in fatty molecules called lipids.  And the membranes that surround cells and their inner compartments are made out of lipids, so chloroquine and hydroxychloroquine can go almost wherever they want in your body; Including into red blood cells.
And you know what else likes to hang our in red blood cells?  The parasites that cause maleria!  
And it just so happens that chloroquine and hydroxychloroquine are also weak bases.  In other words, they like to snatch up protons when they can.  Like the hydrogen ions that make solutions acidic.  And once they do this, they lose their ability to pass freely across membranes.  They're no longer all lipid soluble like they used to be.  
And that means that these drugs can get into acidic places, but they can't get out of them.  So they accumulate in the parts of cells that are acidic, it's pretty cool chemistry.  
And experts think this is ultamately how they kill malaria parasites.  
A bunch of the drug ends up trapped in a stomach-like compartment within the parasite, and interferes with the parasite's ability to break down poisonous substances.  And BOOM! You got yourself a dead parasite.
But killing malaria parasites isn't all these drugs are good at.  Since they (chloroquine and hydroxychloroquine) can get into cells in general, not just the ones infected by parasites; they can have a lot of other effects in the body, including in the immune system.
That's why they work well in a variety of autoimmune conditions.  These conditions manifest in a ton of different ways, but all of them are caused by the immune system going haywire and attacking the body's own cells.  
And while, much like with maleria, we don't fully understand how these drugs help; we do know that they can help calm the immune overreaction.  A big part of that probably comes from their effects on compartments inside your cells, called lysosomes.  
A lysosome's big job is to gobble up and destroy rogue proteins and other compound sthat might be harmful to the cell.  And because they have all those bits of rogue protein, they're able to help some of our immune cells tell other immune system cells what to do.
Basically, the smaller chunckes of protiens and other stuff they break down become antigens; compounds that tell the immune system's soldiers what to go attack.  
It's thought that when a person has an autoimmune condition the lysosomes inside certain immune cells produce antigens that tell the immune system's soldiers to attack the wrong things, the body's own cells. 
But these antimalerials can interfere with that.  Since lysosomes are slightly acidic, hydroxychloroquine makes it's way inside of them and then gets stuck there.  It ends up taking a lot of hydrigen ions out of the lysosome fluid, making it less acidic.  And once the PH of the lysosome gets nice and basic, it can't function in the same way.  Which ultamately, means there are fewer lysosomes generating antigens that tell the immune system to attack the person's own cells.  But, this does not just happen in the cells involved in self directed attacks.  These drugs can get into and mess with all of your immune cells.  
Plus, they likely have other effects in immune cells that can calm them down.  So, they dampen the immune response In General.  
Now, if it sounds like dampening the immune system would be, ya know, actually very bad for a person who has COVID-19; well, you might be wrong.
Here's the thing about a lot of deadly viruses, including coronaviruses; it's not always the virus that actually kills.  Don't get me wrong, the viruses definiately infect cells and kill them.  But it is'nt always the infected cells dying that kills a person- not directly anyway.  
When those cells die, your body realizes there's an invasion taking place.  So, it mounts a counter-attack using chemicals called cytokines, which act as a call to arms to immune cells; raising a battle cry that unleashes the full force and fury of the immune responce on the infection.  
All of the effects of this are collectively called inflamation; and it can do a great job of stampng out an invader.  The trouble is that massibe amounts of inflamation can damage healthy cells too.  So if a viral infection gets really out of control and kills lots of cells, the immune system's frenzied reaction may damage and kill even more cells, which call in even more immunological attackers, which causes even more inflamation. 
If this whole process spirals out of control, it's called a cytokine storm.  It's basically the immune system equivalent of trying to kill a fly with a hand grenade.  And it's the collateral damage from that, that ends up killing the person.  
So it's thoght that a drug like hydroxychloroquine, which eases up the immune responce, might be able to quell a cytokine storm.  At least, that's one hypothosis.
Another idea is that chloroquine and hydroxychloroquine make it harder for viruses by raising the PH in cellular compartments they need to infiltrate and replicate.  Viruses tend to opperate best when these compartments are a little on the acidic side, and antimalarial drugs tend to make things nice and basic.  And there's already some promising reasearch in cells and non-human animals that suggests chloroquine can prevent viral replication in SARS and other coronaviruses.
Even better recent in vitro studies (or experiments carried out in cells in a labroratory) suggest it and hydroxychloroquine might work against SARS-COV-2 specifically, the coronavirus that causes COVID-19.  
Based on this, it seems like these drugs could be super helpful; and a super helpful drug is kind of on everybody's wish list right now.  
But studies of drugs on cells in petri dishes or in other animals are not the same as clinical trials in people.  Just because something works in a controlled lavoroatory enviroment doesn't mean it's gonna be effective in the complicated mess that is the human body practice and that it will be safe for everyone.  
That's what clinical trials are for; to figure that kind of thing out, so we don't end up killing people when we're trying to save them.  
And while it would be amazing if these drugs help, right now we just don't have enough hard evidence that these antimalarials are safe and effective for COVID-19 to start, just like, giving them to everybody.  
Some preliminary data from China suggested that they might help, along with one very small trial out of France.  But some experts have pointed out that that trial has methodological flaws and doesn't provide sufficent evidence.  And a similar trial from China found there was no significant difference between COVID-19 patients that recived hydroxychloroquine and those who didn't.  
Mutiple reasurchers have now concluded that additional, well designed trials are needed before we can really say whether antimalarials are actually safe and effective in fighting COVID-19.  
And I keep saying safe, because even thought these drugs are perscribed regularly for malaria and autoimmune conditions, that dosen't mean they're safe to use in treating coronavirus infections.   
We already know that not everyone can take these drugs safely.  Like people who have a G6PD deficency can have life threatening reactions to chloroquine.  Also, these antimalerials might negitively ineract with other drugs a person is on.  
For example, studies have found that these antimalerials seem to slow the breakdown of the heart medication digoxin, which can case everything from nausea and vomiting to irregualr heart rythems, which can be fatal.  
Plus, even in people who don't have specific reasons not to take them antimalerials aren't totally harmless.  Since they pretty much ubiquitously get into and mess with cells, the dose Really matters.
Like, for example, although chloroquine and hydroxychloroquine can be taken safely by many people, higher doses can lead to blindness and heart problems.  In the end it is possible, that at least one of these drugs really will be great for treating or maybe even preventing COVID-19.  There are several clinical trials trying to figure that out.  And I think everyone really, really hopes that  they will work.  I mean, how amazing would it be if we already have something on hand that kicks this virus's butt?  Something that we understand and that is inexpensive to manufacture.  
But until we know for sure, we should not get our hopes up too much.  We have to let healthcare professionals and medical reasearchers test this stuff carefully and rigorously.  They are the experts and they know what they're doing.  And we have to keep exploring other treatment options, AS MANY OF THEM AS WE CAN.
So thank you to the reasurchers all over the place who are doing that right now.  
Thank you for watching this episode of SciShow News!
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*outro music*