COVID-19 Medication Treatment Trials, Global Testing Remains Limited (lecture 33)
Welcome to another MedCram covid-19 update. This is for Monday, the 9th of March. Here in orange, mainland China’s cases are leveling off. The total recovered is increasing mainly because of the numbers generated from mainland China, but at other locations, we are starting to see things pick up as well.
If we look at the country-specific statistics, we can see of course China at the top, but interestingly if we look at South Korea and Italy, these are two very comparable countries here in terms of total cases. If you look at their populations, total cases per 1 million, they’re also similar: 145 versus 122. We know however that South Korea has done aggressive testing. Close to 200,000 people have been tested in that country.
So I believe what you’re seeing here, with close to 200,000 people being tested, this number is probably pretty close to people who are actually infected in that country. Whereas in Italy, this may represent more of a tip of the iceberg.
As a result of that, we can see that potentially explain here is the total deaths. If the virus is having the same effect in both countries, and at the healthcare delivery systems in both countries are similar, you would expect total deaths here to be similar. Serious and critical, that’s another category where there is a serious difference (between South Korea and Italy).
The big news in Italy is that they are taking what they call exceptional measures to contain about 16 million Italians living in 14 provinces in the north of the country, as well as restrictive measures covering the whole of the country. You can see here in those areas, we have travel being restricted; gatherings, all schools and universities, are closed; all museums and places of culture will be closed; all religious festivals and events are suspended. You can see cinemas, pubs, theaters, etc. etc. Any places where people congregate are being severely restricted or closed.
In the United States with more testing, we’re going to see an explosion here, I believe, of people that are going to be positive, and you can see all of those here listed at Worldominator.
Okay, we’ve received a lot of questions about covid-19 treatment possibilities that may be on the horizon. Medications like remdesivir that we discussed in our Video Update 11 that have shown promising results in a test tube and are in clinical trials with humans as we speak.
Here’s a paper that was published on February 24 that gives more information about how remdesivir actually works. We will put a link in the description below. This medication had gone through phase one trial already, had gone through phase two trials where they looked at safety again except in a larger population.
But when they did the phase 3 trials on Ebola, it did not work. So even though you can get something that works in vitro, it doesn’t always mean it’s going to work in vivo. You have to go through those phase 3 trials before the FDA will give it a label.
Well, the fortunate thing about this medication is it past phase 1, phase 2, so we know it’s a medication that’s relatively safe, and it’s sitting on the shelf for a job to do.
Now enter this covid-19 situation here at the beginning of 2020, it’s being put to work directly into a phase 3 trial. So the nice thing here is that it didn’t have to go through Phase 1 and 2 because it already did that.
Before we continue to talk about remdesivir, we need to follow up on what I illustrated in our last video, Update 32, about how the SARS-cov-2 virus, which causes covid-19, actually hijacks our cells. Something called RNA-dependent-RNA-polymerase, or RdRP for short, is essential for the replication of RNA viruses. Please go back and watch this video so you have context.
在继续谈论瑞德西韦之前，我们需要跟进我在上一个视频Update 32中说明的内容，即导致covid-19的SARS-cov-2病毒实际上如何劫持我们的细胞。 RNA依赖性RNA聚合酶（简称RdRP）对于RNA病毒的复制至关重要。请返回并观看此视频，以便您了解具体情况。
So let’s zoom in and look closely at the function of RdRP because that’s going to tell you why remdesivir may or may not work. So here’s our RNA-dependent-RNA-polymerase, and here’s our viral RNA. You can see the nucleotides here AUGCGCU.
What RNA dependent RNA polymerase is whenever they see an A on the first strand, it will create a strand that has a U. Whenever they see a U, it will put in an A. Whenever they see a G, it will put in a C. Whenever it sees a C, it will put in a G, and so forth and so forth. The way that this works is it always creates RNA from the five prime end to the three prime end, which means that it’s reading the template RNA from the 3 prime end to the 5 prime end.
So here it’s coming up to the next nucleotide, and there are these things floating around, and they have three phosphates on them. All of them have three phosphates. And so the way that this is abbreviated as they’re floating around in the cytosol.
For instance, if this is an A, this would be known as adenosine triphosphate, or ATP. This one here would be known as UTP. What happens is as these nucleotides, which are just floating around in solution, there’s a spot that opens up. Because this is a G, one of them that has a C on it, and three phosphates, will nicely bind in here, and it will form C, and it will continue to go on.
I’m just going to erase some of this here so that we can see it a little bit more clearly. The thing that’s really interesting about this is when it comes to the time when there is a U that opens up, ATP should normally go in there. Remdesivir, as will abbreviate RDV, with a 3-phosphate on the end of it, actually binds into this U state better than the A, and so it will go in there instead.
Here’s the nice thing about RDV in the situation. As soon as RDV binds, as this RNA molecules being copied, about three or four nucleotides down the line, it causes the RNA dependent RNA polymerase to stop. It arrests RNA dependent RNA polymerase.
If you scroll down to the bottom, you can see that remdesivir triphosphate is very similar to adenosine triphosphate. Look at the structure. It’s going to fit very well inside of that spot as the RNA dependent RNA polymerase is going by. But if you have a concentration of RDV-TP in the cytosol, it will suck one of those in and arrest elongation. If you arrest elongation of the RNA, you can’t make viruses, and you stop the infection and its tracks. So you can see why this medication has a lot of promise. But again we have to do the randomized placebo-controlled trials, and those are underway as we speak.
Thanks for joining us.