Coronavirus – Indomethacin to the rescue?

In the X-Files they said “the truth is out there”. What if it was, but it was being drowned in all the chatter about coronavirus?

This morning a patient shared a research paper with me. It’s so relevant I thought I would share it with you. It’s a truth, it’s out there, but nobody seems to be taking notice…

No, this is not a conspiracy theory blog. This is a “here is a good safe drug readily available that seems to work on conronavirus” blog.

On my TODO list is to write an article about what science has in its bag of tricks with respect to protecting us from this virus. The answer is that we have 3+1 strategies where the +1 is repurposing existing drugs.

If you consider an antibiotic like amoxicillin it will kill Gram-positive cocci (say in a Strep throat) and Gram-negative bacilli (say in an E.coli UTI). What those words probably don’t mean much suffice it to say these are very different germs, and yet they share conserved structures we can, and do, target with drugs to kill them.

If most antibiotics are broad-spectrum (kill many things) it should come as little surprise that many of our existing antiviral drugs have activity against more than one virus. Tenoforvir, for example, is used for both HIV and Hepatitis B (HBV). This broad spectrum exists despite the fact HIV is an RNA virus (one sort of genetic code) and HBV is a DNA virus (the other sort of genetic code).

So why are some drugs approved for one purpose and not others they are suited for? It really all comes down to commercials. If the market space for one use of a new drug is crowded the manufacturer might choose to market it for a secondary action that it also works for.

A case in point would be Zyban (Wellbutrin, Bupropion) which, depending on which country you live in may be approved for smoking cessation or the treatment of major depression or both. In Australia it is only approved for smoking cessation so if I want to prescribe it for depression a) it is not subsidised by our Medicare system and b) it is being used off label. That’s despite the fact it works well for some people and is used for exactly that in other countries.

Viagra actually started off as an anti-angina drug for people with chest pain on exertion. When researchers noticed an interesting side effect Pfizer decided to stop the angina research and focus on getting approval for a rather different use. The rest, as they say, is history.

So the fastest path to useful treatments for Coronavirus (now called SARS-CoV-2 for the virus and COVID-19 for the disease) is to repurpose some of our existing drugs. Here is an article from Nature called Coronavirus puts drug repurposing on the fast track.

The beauty of repurposing is that we know how to make these drugs, we know how much to give and we know they are generally safe in humans. The time frame to get approval for a new use is much shorter than the time frame to get approval for a whole new drug it makes a lot of sense.

Which brings us to the point of this article. While the rational drug design people who model how drugs work using supercomputers predict roughly 1/2 of all our antiviral drugs will have some impact on Coronavirus that, to me, seems pretty obvious. Of course, some of them will work!

While this is good, many of the antiviral drugs mentioned are either out of production, in limited production, have significant side effects, or are very expensive. Very few of them outside Lopinavir/Ritonavir or Chloroquine derivatives have any real-world research evidence either. Yes, we are working on testing them but…

What if there was a widely available drug that had been shown to work in both a test tube and dogs? What if it was also cheap and easy to make? How good would that be?

Yes dogs are not people but they are part of the usual path to human testing which looks like test tube -> mice and rats -> small mammals -> large mammals (like dogs) -> primates -> humans.

Indomethacin (Indocid) is a potent Non-Steroidal Anti-Inflammatory (NSAID) drug usually used to treat pain. It’s in the same class of drugs as ibuprofen (Neurofen). It turns out, that back in 2006, some researched has a look at how Indomethacin performed against SARS. The title of the paper kind of gives away the results.

Indomethacin has a potent antiviral activity against SARS coronavirus.

Now SARS from back in 2003/4 is not exactly the same as SARS-CoV-2 but it is very similar. Will this drug that worked in a test tube and in dogs against SARS work in humans against SARS-CoV-2. The answer is that nobody knows but I’m thinking that if I got a bit feverish, had a headache and had a cough I might just leave the aspirin on the shelf and use some indomethacin instead.

We do know it’s safe in people and it does a good just as a pain killer so there is not a lot to lose.

Just my 10c and subject to being proven snake oil but it seemed worthy of a share. On that note, can you share it too? Right this second this old research paper seems to have been drowned in the noise.

Then again, indomethacin is an old drug, first patented in 1961 so anybody can make it and sell it. With no money in proving it works, I can understand the focus on more profitable opportunities but if there was ever a time to put people before patents and profits now would be it.

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