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  • 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 aboutlink

  • 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 sameit'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 helpso 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 thatat least in the labinterferon-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 disposalfor

  • 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 ]

This episode was filmed on April 14th, 2020.

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