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Uploaded:2020-04-17
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About a combination of chloroquine and hydroxychloroquine: https://www.youtube.com/watch?v=va6j4JITJoE

our COVID-19 playlist: https://www.youtube.com/playlist?list=PLsNB4peY6C6IQediwz2GzMTNvm_dMzr47

It will probably be at least a year before we have a vaccine for COVID-19. But in March, the WHO launched a megatrial tolook at four treatment options for the virus.

Hosted by: Hank Green

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Sources:
https://www.healthline.com/health/coronavirus-vs-sars
https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments
https://www.sciencemag.org/news/2019/08/finally-some-good-news-about-ebola-two-new-treatments-dramatically-lower-death-rate
https://stm.sciencemag.org/content/9/396/eaal3653?utm_campaign=toc_stm_2017-06-28&et_rid=17050501&et_cid=1410533
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https://www.nejm.org/doi/full/10.1056/NEJMoa1910993
https://www.sciencedirect.com/science/article/pii/S016635422030200X
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https://www.sciencemag.org/news/2020/03/did-experimental-drug-help-us-coronavirus-patient
https://www.gilead.com/purpose/advancing-global-health/covid-19/remdesivir-clinical-trials
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Image Sources:
https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2#/media/File:Novel_Coronavirus_SARS-CoV-2.jpg
https://en.wikipedia.org/wiki/Chloroquine#/media/File:Chloroquine.svg
https://en.wikipedia.org/wiki/Chloroquine#/media/File:Chloroquine.svg
https://www.istockphoto.com/photo/abstract-molecule-network-background-gm1182803723-332285822
https://en.wikipedia.org/wiki/Lopinavir#/media/File:Lopinavir_ball-and-stick.png
https://www.istockphoto.com/photo/wireless-network-connection-technology-background-concept-hexagon-shapes-pattern-and-gm1073060068-287201199
https://en.wikipedia.org/wiki/Interferon_beta-1a
https://www.istockphoto.com/photo/laboratory-gm1125655473-296013301
This episode was filmed on April 14th, 2020.

If we have more recent episodes on COVID-19, we'll include them in the description. [♪ INTRO ]. It will probably be at least a year before we have a vaccine for COVID-19, the disease caused by the novel coronavirus SARS-CoV-2.

But researchers are hopeful that we won't have to wait that long before we have any treatment, and they're looking into a bunch of options. In March, the World Health Organization, or WHO, launched a megatrial they're calling. SOLIDARITY.

It plans to look at four treatment options for the virus, and hopes to enroll thousands of patients around the world. One is a combination of chloroquine and hydroxychloroquine, which we've already got a video about — link up there and in the description. But there are reasons to be optimistic about the other three.

Here's how they might work. Only one of the treatments in the megatrial involves a single drug on its own. It's called remdesivir, and it's an antiviral drug that was originally trialed as a treatment for the disease caused by the ebolavirus.

While it hasn't panned out for ebolavirus, it has shown promise in lab studies and animal trials on coronaviruses. Almost all of these studies, though, predate this disease. Still, the theory behind remdesivir makes a lot of sense: It blocks the mechanism some viruses, including coronaviruses, use to copy their genetic material and reproduce.

Coronaviruses are RNA viruses, meaning their genetic code is written in RNA molecules instead of DNA molecules. RNA is different from DNA in a lot of ways, but the basic idea is the same — it's a molecule made of building blocks that tell the virus how to make proteins. And when viruses reproduce, they copy the genetic code in their RNA to stick it in the new virus.

That copying is done by a specific type of enzyme known as a polymerase. Part of its job is to pick up each building block to string together the new RNA molecule. Remdesivir interferes with that by pretending to be one of those building blocks, a molecule called adenosine.

Except it's not adenosine, and when the polymerase picks it up and adds it to the. RNA molecule where an adenosine is supposed to go, eventually, the remdesivir breaks the. RNA.

So the new virus can't get a full genome, and can't continue spreading within the body. Conveniently, human cells don't use this mechanism, so theoretically, remdesivir shouldn't be too harmful to us. Human trials haven't found remdesivir to be as effective against ebolavirus as other treatments.

It may be that that virus's polymerase just wasn't fooled. But it does seem to effectively target the polymerases used by coronaviruses, at least in lab and animal tests. And a few studies, like one published in Nature in February 2020, found that the drug does block the virus in a lab environment.

There were also some early case reports of patients with COVID-19 who were treated with remdesivir and recovered, but that doesn't tell us much without controlled trials, because people do often recover from COVID-19. And in a study published on April 10 in the New England Journal of Medicine, 36 out of 51 patients who took remdesivir showed improvement after ten days. But this was what's called a compassionate use program.

It's a way to get patients unproven treatments doctors hope will help — so it lacked the controls researchers would like to see in a true clinical trial. All that has made it one of the WHO's top candidates for its megatrial. And a whole bunch of other human trials are also being run at the same time.

At least two more studies, both being conducted in China, are expected to finish sometime before May. Another part of the WHO megatrial involves a combination of two other antiviral drugs: lopinavir and ritonavir. Both of these are a type of drug called an HIV protease inhibitor.

Proteases are another class of enzyme used by many viruses. The lopinavir-ritonavir combo blocks that enzyme in HIV, which is why they're classified as HIV protease inhibitors. More specifically, lopinavir's role is to block the HIV's protease enzyme, which interferes with the virus's replication process.

Problem is, when the drug is used on its own, one of our own enzymes breaks down the lopinavir too quickly for it to work, so the ritonavir's job is to block /that/ enzyme and save us from ourselves. Coronaviruses have similar protease enzymes that are also a key part of their replication process. So researchers figured the same drug combo might work on them, too.

And in a 2015 study on marmosets infected with the coronavirus that causes MERS, it did seemed to help. A small human trial of about 200 COVID-19 patients in China didn't find an obvious difference when the lopinavir-ritonavir treatment was added to standard care. But when they looked at the numbers more closely, they noticed that there was a bigger difference in the mortality rates when the patients were treated with the drugs within twelve days of their initial symptoms.

They also found that those who got the drugs had fewer serious complications, and not as many of them needed a ventilator. So although the findings were pretty modest, the WHO thinks it's worth a shot. And it helps that since lopinavir and ritonavir are already mass-produced for treating HIV, it's something we could probably roll out very quickly if it turns out to be effective.

Finally, another branch of the megatrial is testing the lopinavir-ritonavir combo plus a protein called interferon-beta. Interferon molecules are a natural part of your immune system. When the immune system detects a viral infection, it starts producing more of these interferons to help kickstart the virus-fighting process.

In that same study that looked at lopinavir and ritonavir in marmosets with MERS, the researchers found that interferon-beta on its own also seemed to work. Another study, published in 2004, found that — at least in the lab — interferon-beta slowed replication in the coronavirus that causes SARS, which is related to the virus that causes COVID-19. When it comes to combining lopinavir, ritonavir, and interferon-beta, a study published in.

January 2020 found that it didn't work very well for treating MERS in mice. But humans are not mice, and there are some differences between the coronaviruses that cause MERS and COVID-19 that could end up being important here. So the WHO thinks there's enough evidence for the three-treatment combo to include it in their megatrial.

There's no guarantee any of these potential treatments or combinations of treatments will work. But there are reasons to study and develop them. It's a glimmer of hope that we can slow this thing down before we have a vaccine.

It's not like science can only do one thing at a time, after all. And there's no specific end date for this trial; rather, the WHO is planning to make adjustments on the fly, discontinuing drugs that don't work and maybe even adding more. Hopefully, we'll start to hear results fairly soon.

Even if these treatments don't work, we might learn more about using them to fight other types of infections. It's all in the interests of having as many tools as possible at our disposal — for this pandemic and the next one. Thanks for watching this episode of SciShow.

We hope you're all staying safe, and we're doing our best to help you understand the science of what's going on right now. We recently compiled all our COVID-19 episodes into a playlist, which we'll link in the description. We're especially grateful to our patrons right now for helping us bring these updates to all of you.

If you'd like to help too, check out patreon.com/scishow. [ ♪OUTRO ].