I've been quite interested in this drug ever since I read in NEJM that the first patient to be diagnosed as SARS-CoV-2 positive in the US ("Snohomish"), was treated under an EUA with remdesivir when they thought he was going south, and the next day, he got better. Much better. Supplemental oxygen was discontinued that day. There is plenty of anecdotal evidence on the web in addition to Snohomish. I read a piece about an ER doc the other day but I can't find it now. The patient said "that magic juice works, Doc."
Remdesivir has a weird name. Many drugs do. In this case, it's a result of a naming convention that antivirals end in -vir, monclonal antibodies in -mab and so on. It's a very useful convention because one can immediately tell the class of a drug from its name. There's a whole list of them here. I don't know that remdes- is significant itself.
Like many antiviral drugs, remdesivir is a nucleoside analog. Here it is compared with ATP (remdesivir on the left, adenosine triphosphate on the right).
Remdesivir was initially developed for Ebola and Marburg viruses (filoviruses). It has broad antiviral activity (in vitro) for other virus families including paramyxoviruses and coronaviruses such as the first SARS-CoV. These viruses are all RNA viruses, and remdesivir inhibits the enzyme that replicates the genome, which is an RNA polymerase.
As part of its clinical testing for Ebola, the safety profile in humans is known to be good, although there are some things to watch for.
As with all antivirals, it is likely to be most effective if given early in the disease. The problem with that is that there doesn't seem to be much of it. The maker, Gilead Sciences, just contributed its entire stockpile of 1.6 M doses to the federal government, and they are busy sending most of it states that voted for Trump (I'm not kidding).
Remdesivir is apparently hard to make. Here is an article about some chemists who were able, with a lot of effort, to synthesize one gram of it. Although you can take that with a grain of salt (or a shot of tequila). This story has twists and turns in it.
Gilead
So Gilead is a company started in the late 1980s, the time when many people including my former professors John Abelson and Mel Simon had a startup to find drugs active against reverse transcriptase. It is named after the Balm of Gilead.
Gilead developed a couple antivirals in the 1990s, and then (small world department) acquired a company called NeXstar Pharmaceuticals in Boulder (this is Larry Gold's company, another colleague from the phage T4 world). If I'm reading wikipedia right, NeXstar was their key acquisition because they obtained a sales and marketing ability for Europe and other markets.
In any event, Gilead is the fish that keeps eating other fish its size or even a little larger, exactly the right ones, and then gaining weight. Big enough to give away a lot of money. According to the wikipedia article, "Charitable donations to HIV/AIDS and liver disease organizations totaled over 440 million in 2015."
One of the companies they acquired had developed sofosbuvir, an antiviral for Hepatitis C virus. They paid 11 B and yet Forbes calls it ""one of the best pharma acquisitions ever".
You may have heard about these treatments. HCV (hepatitis C virus) is essentially a death sentence. Gilead's drug will cure you, but it'll cost you your house.
the cat story
So finally, there's a weird tie-in with cats, which I read this morning in the Atlantic. (In fact, I've been so impressed with them, especially recently, that I purchased my first magazine subscription since Mad magazine).
Apparently remdesivir has a cousin, a closely related drug called GS-441524, also developed by Gilead. It was discovered by a research scientist working on the disease FIP, that GS-441524 cures cats of this fatal GI illness, which is caused by a coronavirus. Apparently, in spite of the pleas of legions of cat-lovers, Gilead will not try to license GS-441524 for this purpose, apparently because
any adverse effects uncovered in cats might have to be reported and investigated to guarantee remdesivir’s safety in humans.So there is a shady black market in China for GS-441524. I kid you not. Read the story, it's great stuff.
Summary
This is just my two cents, which means little. I am highly skeptical that a vaccine can be successfully developed in 18 months, let alone 6. As I said in another post today, the optimistic experts say "maybe we will get lucky."
But I am very optimistic about therapeutics and particularly remdesivir, given early. The thing about COVID-19 is that the lung damage is so severe. Even if you survive it takes a long time to heal. And antivirals always work best given early. See oseltamivir (another Gilead drug).
