28 February 2021

Sunday morning perusals

It was Johnny Cash's birthday last week. I have been a fan from early teenage years after I had stumbled on that recording of the concert in Folsom prison late one night when I had sneaked down to watch tv after everybody had gone to bed. In the 1970s, surrounded by serious Genesis, King Crimson, Led Zeppelin etc. fans, that infatuation was not something to share in public.

Oh. What we considered as troublesome then.

Whereas these days . . .

There's the vaccines, which seem to provide immunity of sorts - very hopeful first data - as well as mild disease course if infected and the potential - highly likely but too early to call - of limited or even halted transmission.

And then there's treatment options. Here is my brief and unskilled summary of a brand new publication on promising drugs to help those infected to recover.

For the full article click here.

SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic, in which acute respiratory infections are associated with high socio-economic burden.

As a complement to the safe and effective vaccines against SARS-CoV-2, the repurposing of existing drugs represents a pragmatic strategy for the treatment of COVID-19 patients. Drug repurposing (drug repositioning) is advantageous in the face of rapidly-spreading emerging diseases.

Multiple ... clinical trials have been initiated in the search for effective treatments against SARS-CoV-2. The individual drugs or combination treatments for these studies have often been selected based on known activities against SARS-CoV, Ebola virus, HIV or Plasmodium spp. ... However, the search for effective drugs against SARS-CoV-2 could extend beyond known antivirals and anti-infectives ...

 A team of virologists, microbiologist, pharmacologists, infectiologists etc.

... applied high-content screening to a well-defined collection of 5632 compounds including 3488 that have undergone previous clinical investigations across 600 indications. The compounds were screened by microscopy for their ability to inhibit SARS-CoV-2 cytopathicity in the human epithelial colorectal adenocarcinoma cell line, Caco-2. 

Cytopathicity is the ability of a virus to produce detrimental changes in cells. So here, over five thousand established drugs (compounds) that have been used and investigated for their efficacy in six hundred diseases were introduced, separately, to a specific human cell line. This cell line has been used in many drug investigation as it shows how and how fast a drug may enter the body via the small intestine. Basically, the Caco-2 cells are our stand-in in drug trials.

If you are not put off by detailed method descriptions of drug testing and the specifics of testing assays and all the technical stuff, this article reads like a thriller where step by step the villain is surrounded by the good guys.

First, anti malarial drugs:

Among the first group of drugs initially reported to show activity against SARS-CoV were anti-malarial compounds such as chloroquine and its close relative hydroxychloroquine, although larger ...  trials indicated they were largely ineffective. We found that ... other anti-malarial compounds ... were inactive ... whereas the chloroquine analog mefloquine showed concentration-dependent activity at the highest compound concentrations.

Next, anti fungal drugs:

 Our hits also included ... anti fungal compounds  all showing ... effective concentrations ...

Then the HIV drugs: 

Several drugs .. developed for the treatment of HIV ... suggesting a possible mechanism for inhibiting viral replication.

Then a couple of others: 

(drugs used) ... for heart disease, impotence, and psychosis, which also inhibit multiple strains of influenza virus (and those) ... with anti cancer activity (and those) ... developed as oral drugs for the treatment of cancer or inflammation.

And, with stubborn dedication (my interpretation) they came closer and closer and - tada! -

...identified 258 hits that inhibited cytopathicity by more than 75%, most of which were not previously known to be active against SARS-CoV-2 ...

I don't have the first clue about what and how they did all this but I am beginning to love science. 

As a side note, the promising drugs may include viagra. Not that it matters to me.



  1. the 'detrimental changes' in cells by a virus is what allows the virus to replicate itself? and so these 258 old drugs stopped that process by 75%? and by doing so prevents the virus from rapidly taking over giving the body's immune system time to marshal it's forces to fight the virus? have I got that right? also, are they doing any studies on the long haulers, the ones with mild symptoms that never seem to go away and why that is? thanks Sabine. I appreciate your making this understandable for the rest of us. but viagra? I have an image in my mind of all these male covid patients with a constant hard on tenting the sheet on their bed.

  2. The viagra bit relates to a drug called papaverine which is used to increase penile blood flow among other things - a potency drug of the viagra family.

    The identified drugs will now have to be tested for dosage, treatment approach and treatment duration, long and short term side effects, possible combination treatment etc. A way to go, but things are moving fast.

    Long Covid is getting a lot of attention as time goes on. I have an alert out for that as well and will report.

    The scare info is multisystem inflammatory syndrome in children (MIS-C), a serious condition that appears to be linked to the virus even when the actual infection is initially mild. So far, it's rare, appears to have a genetic component and all known cases have been resolved with steroid treatment but could mean serious effects in later life as kids grow up.

  3. I am confused by all the scientific explanations, but so appreciative of the efforts by the science/medical community for helping us all get through this pandemic. Thank you for keeping your eye on the latest news and documentation. It helps to know that the efforts are large and ongoing.
    Take care there and stay well, Sabine.

  4. LOL that last line! Viagra! Life can be so endlessly absurd.

  5. I took mefloquine many years ago as an anti-malarial prophylaxis, and it has some seriously weird side effects. I would not want it again, given a choice.

    Your post sent me scurrying to find out whether Johnny Cash was dead. I was pretty sure he was, and indeed -- yes. Since 2003.

  6. Thank you for Johnny Cash and Fiona Apple today.

    Thank you for condensing the article to something I can understand. I appreciate these scientific updates.

    On Friday I received my first Moderna shot. The second shot will be a month from now. An achy arm was my only noticeable reaction. Possibly a mild headache and fatigue, but I may have had those symptoms anyway.

  7. Oh what interesting things are happening in labs! Thanks for giving us an overview, because I never would have understand the reports themselves. Sure, keep on giving us updates, as you get them. I'm also a Cash fan, and Just heard a duet with Joanni Mitchell, which I'd never heard before, on the Johnny Cash show. Somehow I never watched his show, nor do I know when it appeared!