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Last updated: July 1, 2020.

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COVID-19 Update 8: Zinc and chloroquine for the treatment of COVID-19?

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Hey everyone. Today we’re going to learn how we might
be able to use chloroquine and zinc in thefight against COVID-19. But before we get started, I would
like to point out some numbers. These are the number of cases
and deaths as of March 16th. I want to point you specifically
to the numbers of South Korea. There, we currently have 8,236 cases. And only 75 deaths. That’s incredibly low. That’s below 1%!What’s happening here?Why are they so good?As we learned in a previous video, case
fatality rate can be calculated as numberof deaths divided by
number of cases, times 100. However, this is not totally accurate
because there are some cases here thathaven’t been cases for long
enough in order to die yet. So this method probably underestimates
the true case fatality rate. However, it’s still a good method
to compare the different countries. So what’s going on?Obviously, South Korea is at war with
the virus as everyone else in the world. Looking at the images that we see from the
media, their methods look a little moredraconian than in other places maybe. This one, also, they’re doing way
more testing than other countries. Thereby they identify cases that
would be missed in other countries. So the denominator in that case fatality
rate calculation is obviously larger thanin other countries. But is that the whole story?What else are they doing differently?We’ve looked into it a bit deeper and we
found that there’s actually a COVID-19central clinical task force composed
of physicians and experts treating theconfirmed patients across the nation. They recently held their sixth video
conference and agreed on some veryinteresting treatment principles
for patients with COVID-19. On this page, we can find a
description of their recommendations. They recommend that patients should either
receive kaletra, which is a combination oflopinavir and ritonavir, or chloroquine
500 milligrams orally per day. In this consensus document from China,
we can also see that they recommendchloroquine. At a different dose,
but still the same drug. What’s up here?So why does chloroquine seem to
be efficient against SARS-KoV-2. In order to understand that we need to
review a little bit of molecular biology. This is the cell. This is the cytoplasm. This is the nucleus. Inside the nucleus, we have DNA
in a process called transcription. DNA is transcribed to create RNA. RNA then leaves the nucleus, goes into the
cytoplasm, and there it’s being modified. There’s a A-A- A tail, and a five-prime
cap that’s being added, and this signalsto the ribosomes that this RNA
is ready for creating a protein. The ribosome moves from the five-prime
cap to the A-A-A tail in a process calledtranslation – whereby
a protein is generated. Now what happens when a
virus infects the cell?This is SARS-KoV-2, it has a lipid bilayer
just like the cell, but it also hasvarious proteins attached to it and
the big fat piece of RNA inside of it. These are the various
proteins off the virus. This one here is called
S-protein or spike protein. The virus uses this protein in order
to attach to the ACE two receptor. The virus then enters the cell and
releases its RNA into the cytoplasm of thecell. Inside the cell, this strand of RNA also
has a five-prime cap and a A-A-A tail, andguess what?The host ribosomes attach to this piece of
RNA and translates it, thereby creates aprotein called RdRP or
RNA-dependent RNA polymerase. Now this RdRP attaches to the A-A-A
tail and copies it in this direction. This creates a negative version of this
piece of RNA, which has the five-prime endon the other side and the
three prime end on this side. Then the RDRP walks over to the other side
again, copies the piece of RNA again, andwhat we end up with is an identical
copy of the original viral genome. What’s interesting is that the
RNA-dependent RNA polymerase sometimesstops early and creates
a shorter piece of RNA. Sometimes it stops here, sometimes it
stops here and creates this piece of RNA. These pieces of RNA are called sub genomic
RNAs, and again, the ribosomes, they thinkthey have to translate
these pieces of RNA. What happens then is you get these
pieces of protein and those are the viralproteins that we’ve seen previously. Now the replicated RNA and the viral
proteins reassemble into a new virus,which is released from the cell
and ready to infect another person. Now check out this – Zinc has been found
to block the RNA-dependent RNA polymerase. Check out this paper titled “Zinc inhibits
coronavirus and arterivirus RNA polymeraseactivity in vitro and zinc ionophores
block the replication of these viruses incell culture”. So here we have a molecule of zinc,
but it’s hard for it to enter the cell. So these scientists, they had to add a
molecule called PT, which is an ionophore. Now, what does an ionophore do?Well, actually it makes the
cell wall permeable for zinc. It grabs the zinc and pretty much
carries it through the cell wall. And here’s what they found,
in their experiments. They use SARS-CoV the
pathogen causing SARS. And they found that if they added more
zinc to their experiments, less viral RNAwas produced. So zinc could actually
block viral reproduction. This RNA here is the product of the RdRP. Now, here’s the explanation why
chloroquine might be effective in thetreatment of COVID-19 because it is
a zinc ionophore in and of itself. In this paper, they used ovarian cancer
cells to prove that chloroquine enhancedzinc uptake by these cells. So what did they find?On the Y-Axis, you can see how much zinc
they detected inside the cells here, andhere. On the X-Axis are increasing
concentrations of chloroquine or zinc. You can see that increasing doses
of chloroquine cause increasingconcentrations of zinc inside the cell. Similarly, more zinc was found inside the
cell with increasing zinc concentrationsoutside the cell and at each concentration
of zinc, this effect was augmented byadding chloroquine to the experiment
depicted by the black bars. Down here, they showed increasing levels
of fluorescence zinc inside the cells. Here we have controls, almost no zinc. With 50 micromolar of zinc. A little more with 300 micromolar of
chloroquine plus five micromolar of zinc. Even more, and much more. So obviously the addition of chloroquine
had a really, really big effect onintracellular zinc, much more
so than just adding zinc alone. That’s it for now. If you want to improve your understanding
of epidemiology, make sure to register fora free Medmastery trial account and
attend our Epidemiology Essentials Course. We’ve just opened it up to trial
users due to the huge demand. So stay safe and talk soon.

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