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  • 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 ]

  • Allright, Everyone is talking about antimalarials

  • and how they're a promising treatment for COVID-19—let's make the case

  • some people are too excited about this,

  • it's going to end the pandemic,

  • if only the scientists would get out of the way.

  • Some people, on the other hand,

  • are reflexively saying that they definitely don'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've 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 they can do so much.

  • But that doesn't mean we know 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.

  • Thatquinein their names comes from the fact

  • that their chemical structure is similar to quinine

  • or, as some call it, “kwih-nihn”.

  • 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 from each other.

  • and both might seem totally unrelated

  • to the autoimmune conditions like lupus that these drugs are regularly prescribed for.

  • But, once you understand what these antimalarials actually do to cells

  • including their ability to fend off parasites and treat autoimmunity

  • their ability to fight a viral infection actually makes a lot more sense.

  • Let's start with the parasites

  • because these drugs were developed as antimalarials.

  • Despite the long history, it's not 100 percent clear exactly how

  • these drugs treat malaria, though we know the big picture:

  • they kill the parasites.

  • The first reason they can do that is because of their chemical structure,

  • these compounds can 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.

  • You know what else likes hanging out in red blood cells?

  • The parasites that cause malaria!

  • 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.

  • All 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,

  • since those areas have more protons up for grabs,

  • and once the drugs bind protons,

  • they can't move back out so easily.

  • It's pretty cool chemistry.

  • And experts think this is ultimately 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 is not all these drugs are good for, though.

  • Since (they) chloroquine and hydroxychloroquine get into cells in general

  • not just the ones infected by parasites

  • they can have a lot of other effects in the body, including ones to the immune system.

  • That's why they work well in a variety of autoimmune conditions.

  • These conditions manifest in tons 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 malaria,

  • 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 compounds that 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 chunks of material 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 thing, the body's own cells.

  • But these antimalarials can interfere with that.

  • Since lysosomes are slightly acidic,

  • hydroxychloroquine makes its way inside of them and gets stuck there.

  • This ends up taking a lot of hydrogen 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 the same way.

  • Which ultimately means there are fewer lysosomes

  • generating antigens

  • that tell the immune system to attack the person's own cells.

  • But, this doesn't 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,

  • y'know, actually very bad for a person who has COVID-19...

  • 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, these viruses definitely infect cells and kill them.

  • But it isn't always infected cells dying that kills a personnot 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 response on the infection.

  • The effects of this are collectively called inflammation,

  • and it can do a great job of stamping out an invader.

  • The trouble is that massive amounts of inflammation

  • 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 inflammation.

  • 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 thought that a drug like hydroxychloroquine,

  • which eases up the immune response, might be able to quell a cytokine storm.

  • At least, that's one hypothesis.

  • 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 operate best when these compartments

  • are a little on the acidic side,

  • and antimalarial drugs tend to make things nice and basic.

  • There is already some promising research 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 laboratory

  • 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 in cells in petri dishes or in other animals

  • aren't the same as clinical trials in people.

  • Just because something works in a controlled laboratory environment doesn't mean it's

  • going to be effective in practice or safe for everyone.

  • That's what clinical trials are forto 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 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 sufficient evidence.

  • And a similar trial from China found

  • there was no significant difference between COVID-19 patients that received hydroxychloroquine

  • and those who didn't.

  • Multiple researchers have now concluded that additional,

  • well-designed trials are needed before we can really say

  • whether altimalarials are actually safe and effective in fighting COVID-19.

  • And, I keep saying safe,

  • because even though these drugs are prescribed regularly for malaria and autoimmune conditions,

  • that doesn'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 deficiency

  • can have a life-threatening reaction to chloroquine.

  • Also, these antimalarials might negatively interact with other drugs a person is on.

  • For example, studies have found that these antimalarials

  • seem to slow the breakdown of the heart medication digoxin,

  • which can cause everything from nausea and vomiting to irregular heart rhythms,

  • which can be fatal.

  • Plus, even in people who don't have specific reasons not to take them,

  • antimalarials 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.

  • we don't know for sure whether this drug could make that specific infection worse,

  • or at what point in the course of the illness it might be best to take it.**

  • In the end,

  • it's very 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 all that out.

  • And I think everyone really, really hopes they 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 is inexpensive to manufacture.

  • But until we know for sure, we shouldn't get our hopes up too much.

  • We have to let healthcare professionals and medical researchers

  • 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 researchers all over the place who are doing that right now.

  • Thanks for watching this episode of SciShow News!

  • Before we wrap up,

  • we have two quick notes.

  • First: We're so grateful for everyone who watches this show

  • and helps keep the content coming, especially with everything going on in the world right

  • now.

  • So, thank you to all of you who are watching.

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  • Also, merch!

  • If you're interested,

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  • DFTBA.com,

  • which is our merch provider, is open and taking orders again,

  • but they are not currently shipping out because we are not having people gather

  • in a place to do non-essential work right now.

  • Thanks again, and stay safe out there.

  • [ outro ]

This episode was filmed on April 7th, 2020.

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