Possible COVID-19 Treatments Using Hydroxychloroquine and Quercetin (Lecture 35)
Welcome to another MedCram covid-19 update. We are in a pandemic. Italy has shot up dramatically to 12,000 cases. South Korea is still around 7800. We’ve been looking at those two, wondering what the difference is between Italy and South Korea. Italy has an excellent healthcare delivery system as that of South Korea. Many possible explanations for the differences in those two. Here in the United States, we have a total of 1,300 cases; total deaths 38; total recovered 15; serious or critical cases 10, and that’s around 4 cases per million population.
A number of things have happened politically, which you probably already know about. The President has banned flights in from Europe except for Great Britain. The National Basketball Association has essentially canceled the season at this point. Tom Hanks and his wife, who are in Australia, report that they are infected with the coronavirus. There are a number of new cases here and especially around on the west coast and east coast in cities.
In our last update, we did talk about zinc, zinc ionophores, and the ability of chloroquine to inhibit RNA-dependent RNA polymerase from coronavirus. Essentially, we’re looking at chloroquine and its derivatives as an antiviral medication in prevention. We said that it’s potentially possible that the mechanism that this chloroquine, or hydroxychloroquine, works-through is through a zinc ionophore mechanism.
I wanted to show you this paper that was published just three days ago. It looked specifically at the in vitro antiviral activity and optimized dosing regimen for hydroxychloroquine, which is a better tolerated and more available medication, and chloroquine is for the treatment of covid-19.
They looked at hydroxychloroquine because it’s an immunomodulator. It might be able to attenuate this “cytokine storm”, which is involved with ARDS, which we’ve talked about before. I want to stress that there currently is no evidence to support the use of hydroxychloroquine on SARS-COV-2 infection. We don’t have any randomized controlled trials, and that’s exactly why they are using this medication and trying to figure out appropriate dosing before they are able to start a randomized controlled trial.
So if you look here. They took cells and they incubated them in this medication. They subjected them to the actual SARS-cov-2 virus. They also did it the other direction. They had the virus in the cells, and then they treated them with this hydroxychloroquine in different concentrations.
They also looked at chloroquine as well. The conclusion of the research was that hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-COV-2, and the keyword here is in vitro.
So here’s the data. We can see here chloroquine on the left, and hydroxychloroquine here on the right. As we increase the concentrations of either one, whether or not the drug was there for 24 hours or 48 hours, as the concentration of the drug goes up, the percent of inhibition goes up.
For instance, in the hydroxychloroquine, we were able to see these values going up higher, therefore, inhibiting more virus. Of course, if it was there for 48 hours, we would have seen it inhibiting even more than if it was there for only 24 hours, letting you believe that the drug is starting to accumulate more and more in those first 24 to 48 hours.
You can also see that given hydroxychloroquine at one micromolar at 48 hours, it’s able to hit 50% of inhibition, whereas over here, you need a much higher concentration to hit 50% of inhibition, and that’s exactly what these E numbers are.
So the lower the E number, the better. You can see here for hydroxychloroquine, these E numbers are smaller than the corresponding chloroquine numbers. Down here, they have prophylactic treatment, which means that they were incubated with this medication before the virus was given, and you can see here that the numbers are much better for hydroxychloroquine because the values go up fairly high and they stay up.
In other words, in this case, if you are on hydroxychloroquine for 48 hours prior to infection with the actual coronavirus SARS-cov-2, and it was at this concentration, there would be absolutely no viral replication occurring. The way they did this was using reverse transcriptase PCR.
They also looked at the dosing, and they could see here how often would they need to actually dose this medication. They found that if they gave it for just 4, 5 days, it stayed in the system for quite a long time, and the plasma concentration didn’t decrease, and it was still affected here.
We can see blood concentration not dropping too much, and here in the lung concentration, where it would be needed the most, it hardly dropped at all. It was concentrated in the lungs. So even though it was stopped at day number 5, it is hung around for an additional at least 5 days.
So the overall study results were: based on these models, a loading dose of 400 milligrams twice for the first day, and then followed by a maintenance dose of 200 milligrams given twice daily for 4 days, is recommended for SARS-cov-2 infection. Again, I wanted to mention this because we had talked previously about that, so as hospitals across the country start to see this kind of infection coming in, this may be one type of treatment that you consider.
If the mechanism of action for hydroxychloroquine and chloroquine in vitro in stopping the virus is related at all to the fact that it’s also a zinc ionophore, then the question is obvious: do other zinc ionophores do the same thing? Here’s the zinc ionophore quercetin. This quercetin also does the same thing in terms of increasing zinc intracellularly and blocking viral production.
Here we have some data that was published, and we’ll put a link to this article in the description below. You can see here clearly that when you add zinc in it, increasing concentrations, zinc does get inside the cell. But when you add quercetin, it’s going to increase the amount of zinc inside the cell.
So the next question is: does it actually reduce virus? Again, an in vitro study, quercetin, as an antiviral agent, inhibits influenza A virus entry. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop an effective, safe and affordable natural product for the treatment and prophylaxis of influenza infections. This is not covid-19. This is influenza.
Here we can see that at zero quercetin, we see a lot of viral particles here that are illuminated with the fluorescent antibodies. As we increase the dose of quercetin, you can see that the number of particles decreases rapidly until it’s not seen at all.
As we can see here. There is some evidence that quercetin had already been proven successful at treating Ebola and zika viruses. The question is what’s going on with covid-19? Here, we have a story from CBC, which is the news organization of Canada, spreads speeds up Montreal researchers will trial and antiviral treatment for covid-19 in China. These two researchers here at Montreal are wanting to tests for quercetin in the arena of covid-19. This drug is derived from plants, and you don’t need a prescription for it. You can actually get this over the counter.
Now, in the number of studies that I’ve seen and researched on the internet, this medication was tested in zika and Ebola viruses at a dose of around 50 to 100 milligrams per kilogram, which would mean that you’re talking about three to seven grams a day of this medication, which is just astounding. I don’t know if that’s the dose that is actually needed, but that’s what the studies were showing.
Let’s summarize what we found out here for the zinc ionophores. We may come back to this. First of all, we have no randomized control trials for any of this, so we can’t say that any of this actually works. But the Chinese have just published a paper a couple of days ago, showing that hydroxychloroquine is superior to chloroquine in terms of potency. Their proposed dosing regimen would be 400 milligrams twice a day for one day and then 200 milligrams orally twice a day for four days.
PO means by mouth, that means in the mouth. BID means twice a day. In terms of quercetin, we don’t know. It is over the counter; we don’t know dosing. Again, no randomized controlled trials. This is what they’re actually working on, trying to do at this point.
It should be noted, and there were some questions about this, that if this is a zinc ionophore, question is: should you take a zinc supplement? I think it’s more important that you’re not zinc deficient than it is that you try to boost up your zinc blood levels because again, those are regulated. If you have more zinc in your blood, then you should be having your body’s going to regulate that by trying to get it out of your system and try to pee it out. Of course, that can be overwhelmed if you take too much zinc, so you don’t want to do that either. I think the key here is don’t be zinc deficient. So question on zinc supplements. Thanks for joining us.