There is some anecdotal clinical evidence that chloroquine and hydoxychloroquine may be effective against SARS-CoV-2, which is supported by some tissue culture data. The proposed mechanism of action is the impairment of lysosomal pH. Apparently, proper lysosomal function at low pH is required for viral replication. These drugs may be inhibiting viral replication by increasing the pH of the lysosome.
I am wondering if other drugs that may further increase lysosome pH may potentiate the antiviral activity of HCQ and chloroquine. The pH in the lysosome is maintained by a proton pump. There is already data in the literature suggesting that the commonly used proton pump inhibitors (omeprazole, pantoprozole and lansoprozole ) can impair lysosome acidity. I wonder if adding these widely used and safe medications to chloroquine and hydroxychloroquine may be useful in treating COVID-19. Any thoughts?
Here is an interesting article on an interactome map using the SARSCoV2 proteins as bait and fishing out the human proteins that they prey on. The information was used to identify potential existing drugs and chemicals that may target either the viral proteins or their targets.
https://www.biorxiv.org/content/10.1101/2020.03.22.002386v1.full.pdf
Apparently, Bafilomycin is one of the drugs identified which inhibits ATP6AP1, an ATPase inhibitor. This enzyme was "fished" by using the Nsp6 protein of the SARSCoV2.
As far as I understand, the proposed mechanism of chloroquine and hydroxychloroquine is by increasing the pH of the lysosome and impairing viral fusion and assembly. If this is true, it would be useful to use during the early phase of infection and as a prophylactic agent. Bafilomycin may enhance this activity. I also raised the question if proton pump inhibitors may also have a similar effect. However, I doubt that chloroquine/hydroxychloroquine (HCQ) would have much effect on the cytokine storm, based on our clinical experience with HCQ on rheumatic diseases. It is not a strong inhibitor of any of the cytokines involved. It would require much heavier guns like IL-6 inhibitors (sarilumab, tocilizumab) to calm a cytokine storm.
That is interesting.. The answer above sounds "exactly" like my answer to a similar question about using bafilomycin. As a matter of fact, it is my answer, verbatim! Why would someone copy it and paste it here??
You need to study the possible interaction between PPIs and chloroquine as omeprazole and lansoprazole were shown to be potent competitive inhibitors of CYP2C19 substrates. Would this affect the combination or not? Still questionable and needs investigation. Previous studies on the possible antimalarial effect of omeprazole showed antagonism when combined with chloroquine. Would this also occur in covid-19??
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