Well, after many twists and turns, we ended up here.
This sentence "The inside of the vesicle becomes increasingly acidic, and the membrane of the vesicle and the virus fuse through the viral spike" that is written in this article, I believe that SARS-CoV-2 may delay the entry of viral RNA into the cytoplasm by suppressing the acidification of the endosome.
However, since proton pump inhibitors "act on the proton pumps of the stomach wall cells and inhibit the secretion of gastric acid" (Wikipedia) (usually used for this purpose), there are concerns such as "It has been reported that the inhibitory effect of gastric acid on bactericidal activity may cause changes in the intestinal flora and enhance inflammation of the small intestine" (Wikipedia).
I didn't understand why such drugs are available over-the-counter in the United States yet, but I am aware that these are drugs that need to be managed by a doctor.
Also, it's effect is just the slow down of infection means that in order to cure the infection, you need to use other drugs or wait for the virus to be eliminated by immunity.
In addition, the evaluation of whether there was the slow down of infection cannot be made unless there are evaluation criteria or evaluation methods that can exclude such cases, because in most cases, COVID-19 do not become severe even if there is no slow down of infection. (Even a bad result may not exclude the possibility of other factors.)
In other words, we would like you to understand that you should make a careful decision, as it has possibility to cause no benefit and a lot of harm to try it out blindly at this point.
(1) Keeping the above assumptions in mind, I would like to first describe the possibilities of the principles mentioned above.
The proton pump inhibitors is used to inhibit proton pumps, as the name implies. Since acidification of endosomes is also performed by proton pumps (Wikipedia), it is essential for this principle that assume that the proton pump inhibitors inhibit this proton pumps.
However, the story is not so simple: the proton pumps that produce gastric acid are H+,K+-ATPases, and the proton pumps that acidify the endosomes are V-ATPases, and they are not exactly the same.
Therefore, if the action of the drug is specific for the H+,K+-ATPase (which is also desirable for the original use of the drug), then the above principle does not hold.
So, I would like to accumulate information on this point.
The first thing I was able to confirm was information from a study that looked at whether using proton pump inhibitors to inhibit the V-ATPase in the treatment of cancer could increase the effectiveness of anticancer drugs and other drugs.
Next is information on the use of proton pump inhibitors for the prevention of acute exacerbations of COPD (chronic obstructive pulmonary disease). The strength of the evidence needs to be considered separately, but clinical trials have been conducted and the results are interesting.
(2) Next, we would like to consider what kind of evaluation can be done in the case of COVID-19.
First of all, I think it is one way to search for trends in a given group of people by combining various individual conditions as described below. In other words, this is a way to check whether there is a tendency to have fewer patients with serious illnesses in a group of people who are taking proton pump inhibitors. If anyone can find this kind of information elsewhere, please let me know in the comments.
Since I don't have the chance to do the above at the moment, I will consider the information from the cases of COVID-19 published who are prescribed proton pump inhibitors to see if there is anything distinctive and add to it below. If anyone has found a case of someone who has been prescribed a proton pump inhibitor, please let me know in the comments.
[2020/05/24]
Currently, we have read all the case reports of COVID-19 published by the Japanese Society of Infectious Diseases, but I couldn't find a clear difference between those who take a proton pump inhibitor as a regular drug and those who do not.
On the other hand, in this case report, in addition to treatment with hydroxychloroquine, proton pump inhibitors were given to severely ill patients (it's hard to say at this point whether this is related to the disease or not), with very good results except for one patient who died of bacterial pneumonia. However, this result cannot be fully validated because the details of each of the 30 cases of treatment are not known. This is a shame, as hydroxychloroquine also acts to inhibit endosomal acidification (increase pH) and seems to be a good example of synergistic effects with proton pump inhibitors.
Currently, we have read all the case reports of COVID-19 published by the Japanese Society of Infectious Diseases, but I couldn't find a clear difference between those who take a proton pump inhibitor as a regular drug and those who do not.
On the other hand, in this case report, in addition to treatment with hydroxychloroquine, proton pump inhibitors were given to severely ill patients (it's hard to say at this point whether this is related to the disease or not), with very good results except for one patient who died of bacterial pneumonia. However, this result cannot be fully validated because the details of each of the 30 cases of treatment are not known. This is a shame, as hydroxychloroquine also acts to inhibit endosomal acidification (increase pH) and seems to be a good example of synergistic effects with proton pump inhibitors.
There is a vacuolar proton pump inhibitor that inhibits acidification of endosomes, so we are thinking of collecting information on that as well.
[2020/05/24]
I've checked, and there are no vacuolar proton pump inhibitors that seem to be available for this use. (For reasons such as cytotoxicity.)
I've checked, and there are no vacuolar proton pump inhibitors that seem to be available for this use. (For reasons such as cytotoxicity.)
