使用羟氯喹和槲皮素治疗COVID-19 (新冠肺炎讲座35)

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.

欢迎来到MedCram covid-19的另一个更新。我们正处于大传染病。意大利的病例激增至12,000起。韩国仍然在7800左右。我们一直在研究这两个国家,想知道意大利和韩国之间的区别是什么。意大利拥有与韩国一样出色的医疗保健提供系统。对于这两者之间的差异有许多可能的解释。在美国,我们总共有1,300例;总死亡38;共康复了15人;严重及危重病例10,每百万人口中大约有4例。

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.

政治上发生了许多事情,您可能已经知道。总统禁止从英国以外的欧洲出发的航班。美国国家篮球协会目前已经取消了本赛季。澳大利亚的汤姆·汉克斯(Tom Hanks)和他的妻子报告说,他们感染了冠状病毒。这里有许多新病例,尤其是在城市的西海岸和东海岸附近。

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.

在我们的最新更新中,我们确实讨论了锌,锌离子载体以及氯喹抑制冠状病毒中RNA依赖性RNA聚合酶的能力。本质上,我们正在寻找氯喹及其衍生物作为预防性抗病毒药物。我们说过,这种氯喹或羟氯喹通过的机制可能是通过锌离子载体机制。

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.

我想向您展示三天前发表的这篇论文。它专门研究了羟氯喹的体外抗病毒活性和优化的给药方案,羟氯喹是一种耐受性更好的药物,而氯喹则用于治疗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.

他们研究了羟氯喹,因为它是一种免疫调节剂。它可能能够减弱这种与ARDS有关的“细胞因子风暴”,这是我们之前讨论过的。我想强调,目前没有证据支持在SARS-COV-2感染上使用羟氯喹。我们没有任何随机对照试验,这就是为什么他们使用这种药物并尝试找出合适的剂量后才能开始随机对照试验。

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.

所以,如果你看这里。他们取出细胞,并在这种药物中孵育它们。他们使他们遭受了实际的SARS-cov-2病毒。他们也朝另一个方向做了。他们在细胞中感染了病毒,然后用不同浓度的羟氯喹对它们进行处理。

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.

他们还研究了氯喹。研究的结论是,发现羟氯喹比氯喹对抑制SARS-COV-2的抑制作用更强,此处的关键词是体外。

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.

这是数据。我们在这里可以看到左侧的氯喹,在右边的羟基氯喹。当我们增加一种药物的浓度时,无论药物是否存在于24小时或48小时,随着药物浓度的增加,抑制百分比也会增加。

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.

例如,在羟氯喹中,我们能够看到这些值上升得更高,因此抑制了更多的病毒。当然,如果在这里放置48小时,我们会发现它比仅在其中放置24小时具有更大的抑制作用,让您相信该药物在开始的24至48小时内开始越来越多地积累。

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.

您还可以看到,在48小时内给定一微摩尔羟基氯喹的情况下,它可以达到50%的抑制作用,而在这里,您需要更高的浓度才能达到50%的抑制作用,这正是这些E数。

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.

因此,E值越低越好。您可以在此处看到羟基氯喹,这些E数小于相应的氯喹数。在这里,他们接受了预防性治疗,这意味着他们在感染病毒之前已与这种药物一起孵育,并且您可以在此处看到羟氯喹的数字更好,因为该值会上升并保持上升。

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.

换句话说,在这种情况下,如果您在感染实际冠状病毒SARS-cov-2之前48小时用上羟氯喹,并且处于这种浓度,则绝对不会发生病毒复制。他们这样做的方法是使用逆转录酶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.

他们还查看了剂量,并在这里可以看到实际需要多久给一次这种药物剂量。他们发现,如果只给它4、5天,它就可以在系统中停留很长时间,并且血浆浓度并没有降低,并且在这里仍然受到影响。

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.

我们可以看到血液浓度没有下降太多,在这里肺部浓度是最需要的,根本没有下降。它集中在肺部。因此,即使它已在第5天停止,它仍然挂了至少5天。

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.

因此,总体研究结果是:基于这些模型,建议对SARS-cov-2感染的第一天两次加载剂量为400毫克,然后每天两次维持剂量为200毫克,持续4天。 再次,我想提到这一点,因为我们之前已经讨论过这一点,所以随着全国各地的医院开始看到这种感染,这可能是您考虑的一种治疗方法。

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.

如果说羟基氯喹和氯喹在体外阻止病毒的作用机理与它也是锌离子载体完全相关,那么问题就很明显:其他锌离子载体也能做同样的事情吗?这是锌离子载体槲皮素。该槲皮素在增加细胞内锌含量和阻断病毒产生方面也起同样的作用。

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.

在这里,我们有一些已发布的数据,我们将在下面的描述中放置指向本文的链接。您可以在此处清楚地看到,当向其中添加锌时,浓度增加,锌确实会进入细胞内部。但是,当添加槲皮素时,它将增加细胞内锌的含量。

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.

因此,下一个问题是:它实际上可以减少病毒吗?再次,在体外研究中,槲皮素作为抗病毒剂可抑制甲型流感病毒的进入。这项研究表明,槲皮素在流感病毒感染的早期阶段显示抑制活性,为开发一种有效,安全和负担得起的天然产品用于治疗和预防流感病毒感染提供了未来的治疗选择。这不是covid-19。这是流感。

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.

在这里我们可以看到在槲皮素为零的情况下,我们在此处看到许多被荧光抗体照射的病毒颗粒。随着我们增加槲皮素的剂量,您可以看到颗粒数量迅速减少,直到完全看不到为止。

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.

正如我们在这里看到的。有证据表明,槲皮素已被证明可以成功治疗埃博拉和寨卡病毒。问题是covid-19怎么了?在这里,我们有加拿大新闻机构加拿大广播公司(CBC)的一个故事,它传播的速度加快了,蒙特利尔研究人员将在中国对covid-19进行试验和抗病毒治疗。蒙特利尔的这两位研究人员希望在covid-19领域测试槲皮素。这种药物来自植物,您不需要处方。您实际上可以在柜台上买到。

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.

现在,在我在互联网上看到的大量研究中,这种药物已在寨卡病毒和埃博拉病毒中进行了测试,剂量约为每公斤50至100毫克,这意味着您正在谈论三每天吃七克这种药,真是惊人。我不知道这是否是实际需要的剂量,但这就是研究显示的剂量。

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.

让我们总结一下我们在这里发现的锌离子载体。我们可能会回到这一点。首先,我们对此没有任何随机对照试验,因此我们不能说其中任何一项都有效。但是中国人几天前才发表过一篇论文,表明在效力方面,羟氯喹优于氯喹。他们建议的给药方案是一天两次,每天两次400毫克,然后一天两次,每天两次,一次200毫克。

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.

PO表示通过嘴,即在嘴中。 BID表示每天两次。关于槲皮素,我们不知道。在柜台上;我们不知道加药。同样,没有随机对照试验。这是他们实际上正在尝试的工作。

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.

应该指出的是,对此有一些疑问,如果这是锌离子载体,那么问题是:您应该服用锌补充剂吗?我认为,重要的是您不缺锌,而不是尝试增加锌的血液水平,因为同样,锌的水平也受到监管。如果您的血液中含有更多的锌,那么您应该通过尝试将其从系统中释放出来并撒尿来对身体进行调节。当然,如果您摄入过多的锌,可能会不知所措,因此您也不想这样做。我认为这里的关键是不要缺锌。因此对锌补充剂的问题。感谢您加入我们。

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