Will proton pump inhibitors (PPI) stop the time of SARS-CoV-2

 I am not a medical professional, so there may be some errors or inaccuracies in the information. If you notice such a part, please let me know in the comments.

 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.

 Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors

 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.

 A new strategy with proton pump inhibitors for the prevention of acute exacerbations in COPD

(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.

 Interest of Proton Pump Inhibitors in Reducing the Occurrence of COVID-19: A Case-Control Study

 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.

 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.)

A method for investigating drugs that may increase immunity against the Coronavirus

In considering the response to the Coronavirus, I'm presumptuous to state here that the following investigation may provide clues to the discovery of effective drugs.
Since it takes time for a new type of COVID-19 to become severe from the time of mild illness, I believe that the current situation can be significantly improved by not only discovering a drug that can use at the stage of severe illness but also discovering a drug that can prevent or delay the severe illness by administering it at the stage of mild illness.
As long as we have the data, I can conduct this survey without bothering people who are currently very busy, so I believe that this survey has excellent parallelism and that it is not a bad idea to conduct it even if it is not the best choice.

Purpose: To investigate drugs that may boost immunity

Immunity here is the same as immunity which is used like that "we should try to improve immunity by getting enough sleep and eating a well-balanced diet as one of the measures to prevent infection with the Coronavirus".
To put it simply, this study is an attempt to find out if people who have been prescribed certain medications for some kind of illness are less likely to (for example) catch a cold afterwards, which may indicate that these medications may be boosting their "immunity".

Although it is assumed that human immune function is effective against the Coronavirus (I think it is safe to assume that it is effective if it can be cured naturally), I believe that the following research can be used to investigate whether there are any drugs that may enhance immune function. (With this method, it is difficult to discover drugs that can be administered to critically ill patients that directly interfere with the activities of the Coronavirus, such as the drugs currently undergoing clinical trials, but we thought of this method as a way to explore various possibilities. Therefore, we believe that it is possible to derive information that may lead to the awareness of medical practitioners in addition to the discovery of the desired medicine.) (By the way, there already seems to be something called Inosine pranobex as an immune-enhancing drug, but I think there is a concern such as the rise in the uric acid level, but is there a possibility that this is effective for the Coronavirus?)
The goal at this time is to find a drug that can be administered in the early stages of a new coronavirus. By focusing on boosting immunity, I think it would be best if we could find a medication that can be administered for colds, flu, and new types of coronaviruses (because I think we can judge the prescription even if we don't get a positive test for flu or new types of coronavirus). In order to get to this point, additional verification will be required in addition to this verification, but I believe that this verification will be useful in deciding which drugs should be subject to verification.
Since I am neither a doctor nor a medical professional (I am only a database engineer), please make sure to confirm the validity of the survey from the perspective of a medical professional when conducting this survey.

Verification procedure

Step 1. The following information is extracted from the database of health insurance use under the following extraction conditions

Extraction conditions

1. The information must be linked to an individual. (If family information is mixed, it is excluded from the extraction target.)

2. Being prescribed a medication that needs to be prescribed regularly for a long period of time. (Because I'm concerned that including data that does not fall under this category may include a unnegligible level of noise, such as people who don't go to the hospital even if they are sick.)

Information to be extracted (other information is ignored this time for simplicity's sake)

1. Insurance number (assign a new sequential number so that the original number cannot be pulled. Although it would be better to assign the same number if the same individual is linked to a different insurance number, this is not required because this verification is urgent and treating the same person with a different insurance number as a different person is not considered to be a major problem.)

2. Age

3. Gender (physiological gender)

4. Date of visit (date of prescription) Temporary remove information prior to prescription of medication that requires regular visits (may be used later to monitor changes before and after prescription)

5. Reception region (used to check if there are regional differences in the distribution of features within the group and to add the region to the conditions for grouping if there are regional differences)

6. Medications prescribed (one record for each type of medication, even if prescribed on the same day)

7. Prescription amount (reference information to determine the amount of medicine to be prescribed)

Step 2. Based on the information extracted in step 1, the data are grouped into individual groups under the following conditions

1. Age (for the time being, in 10-year increments. When it is necessary to look at it in detail, it is used in detail)

2. Gender

3. Prescribed medications (categorized by individual who is prescribed medications that require regular visits. (If an individual is prescribed more than one medication that requires regular visits, the individual belongs to more than one group. If the prescription period for the medication that requires regular visits is staggered, each prescription period is the period of time that the individual belongs to that group of medications.) Later, new findings may be obtained by comparing the differences by excluding individuals belonging to more than one group.)

Step 3. Identify the incidence, frequency, and duration of the common cold per period of time for each group

(In the case of outpatient visits, the minimum period of illness is 5 days, and the period of illness is the time spent in the hospital before the cold is cured.) Cold illness is judged from the medications prescribed.
(I have chosen the common cold as a common illness, but if you have any other valid illnesses, you are welcome to change them and verify them.)
(In Japan, a doctor prescripts some drugs (not always but normally) even if it is just catching a cold. So it is possible to know groups of extremely low possibility of catching cold if there is it)

For the mean values of incidence, incidence frequency, and duration of incidence, we discarded both extremes and used the values averaged near the center of the distribution. (Both extremes are not used to make averages, as some medications may include those that make you extremely prone to catching colds.)

Step 4. Based on the above results, the drugs in the group with a significant difference in immunity (additional verification is needed if the population is small) are considered to be drugs with the potential to enhance immunity, and the active ingredients with the potential to enhance immunity are verified and identified, and then the demonstration is carried out in the medical field related to the Coronavirus.

It should be noted that the drugs with the potential to enhance immunity obtained in this verification need to be additionally considered and verified from the following perspectives.
1. Immunity against the common cold has been evaluated, but is it also effective in boosting immunity against the Coronaviruses?
2. Is immunity to the Coronaviruses built up before they become severe (it may take some time for immunity to build up, as long-term prescription drugs are being evaluated)

3. Can we extract an active ingredient that can be administered to a patient with the Coronaviruses?

(Note that some of the identified active ingredients may not be available as-is in medical practice. In this case, it would be necessary to consider whether the active ingredient can be made into an active ingredient that can be used in the medical field, but since this would be a time-consuming process, the use of the active ingredient from the next most likely effective group should be considered.)
4. Is there an increased or decreased risk of Cytokine storms?

Step 5. As soon as the drug is confirmed to be effective in the medical field, it will be approached to the WHO for using worldwide

For this reason, it is preferable that the drug in question is either off patent or has no patent in the first place. (Otherwise, there is concern that the drug will delay penetration and impossible to minimize the damage.)

Attention: The following points should be taken into account when handling the information

1. The work of extracting data from the database of health insurance use (and numbering sequential number) will be done with as few people as possible, while taking the necessary measures to handle personal information. (If possible, it should be carried out by one person.)

2. Although the individual cannot be identified, the data after extraction is still associated with an individual, so the data will be handled strictly and measures will be taken to ensure that it is not leaked to the outside world.

3. When grouping individuals, only groups with a population of 100 or more may publish their results; groups below 100 will not publish their results. (If the total of all ages, the total of men and women, etc., can be 100 or more, it may be published in that unit.)

4. Before verification, the necessary approvals must be confirmed and get approved.

In addition, since this verification method is not limited to this verification and can explore different aspects of existing long-term medications, it would be desirable to develop it as a system that can be used by medical professionals and medical students in the future.

I assume that this will broaden the scope of the use of existing drugs and contribute to the development of medicine and the reduction of medical costs.