DIY Reduction of Ace2 Levels?

Here’s a title for a GEO dataset we espied today: BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2. ACE2 is indeed reduced by BRD2 knockdown in the Calu-3 cells used in this unpublished study. We’ll add the data to our database shortly.

What other drugs/treatments might reduce ACE2 levels? It’s easy to use our “Relevant Studies” tool to get some clues: type “ACE2” in the identifiers box, choose “downregulated” under “Regulation”, and choose “lung” as “Cell type.”

In terms of “do it at home” approaches, it appears that increased selenium might do it. You’ll have to check out the fine details in the underlying study to see if the levels used in mice would be at all “reasonable” in humans: Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice. That’s about it. The three other approaches suggested by the Relevant Studies app are not exactly home-friendly: knockouts of TLR3, RNase L, or transfection of mir-138.

Perhaps bizarrely, there’s actually a study that links inadequate selenium to Covid-19 infection. The sample size was fairly small (30 patients, 30 controls), but an impressive P-value was derived (.0003): An exploratory study of selenium status in healthy individuals and in patients with COVID-19 in a south Indian population: The case for adequate selenium status.

We can eliminate the requirement that the downregulation occur in the lung. In that case, we get 102 approaches! In terms of drugs, there’s cabergoline, GSK3 inhibitors, dimethyl maleate, and a long list of other drugs. Even after eliminating the “lung” requirement, selenium is still the only potential DIY approach.

Of course, transcriptomic results don’t always translate to proteomic results. In terms of proteomic studies, only the aforementioned RNaseL KO is found in the database.

What might increase ACE2 levels? With the “lung” requirement, we see only two results, neither of which suggest that common drugs could lead to inadvertant ACE2 over-expression. Without the requirement, we get 115 results. Interestingly, interferon-alpha treatment might not be recommended as a Covid-19 preventative. Trametinib, metformin, resveratrol, ifn-kappa, antibiotics, dexamethasone, cholesterol, low riboflavin (vitamin B2) levels, and gold ion could also be contra-indicated for folks who are keen to avoid Covid-19. Cholesterol in particular catches our eyes, as many viruses seem to require it to carve out their little lipid-encased niches in or around the host endoplasmic reticulum. Naturally, though, it’s questionable whether dietary cholesterol alterations would have any effect on ACE2 levels in the human lung (mouse hippocampi were examined in the study in question).

Hopefully, we needn’t point out that everything above should be validated in the lab/field. It’s also worth remembering that Covid-19 prevention and treatment are very, very different subjects; potentially diametrically opposed! Both dexamethasone and interferons have indeed been used as treatments for infected patients.

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