
Remdesivir and chloroquine effectively inhibit coronavirus (2019-nCoV) in vitro - guybedo
https://www.nature.com/articles/s41422-020-0282-0
======
toyg
Not just in vitro - Italian media reported today that the two Chinese tourists
who fell ill in Rome have been successfully treated with Remdesivir (freely
provided by Gilead). Source (Italian):
[https://www.corriere.it/cronache/20_febbraio_26/coronavirus-...](https://www.corriere.it/cronache/20_febbraio_26/coronavirus-
guariti-tre-pazienti-curati-roma-farmaco-studiato-contro-l-ebola-fa-sperare-
medici-5c56ad00-58ba-11ea-8e3a-a0c8564bd6c7.shtml)

~~~
koheripbal
While that's good news - it isn't statistically significant.

You need to do a double-blind test to confirm results.

~~~
EForEndeavour
This is an example of real-world evidence
([https://en.wikipedia.org/wiki/Real_world_evidence](https://en.wikipedia.org/wiki/Real_world_evidence)),
gathered outside the context of any kind of drug trial, blinded or not.

While these two outcomes may not achieve statistical significance in the
mathematical sense...

\- there are compelling mechanistic hypotheses for why the treatments might
work

\- drug doses are being supplied for free by manufacturers

\- infected people don't have the luxury of time to wait for RCT results

~~~
AstralStorm
Most importantly, a placebo controlled RCT would be unethical for a disease
with high mortality rates.

You would run a randomized controlled trial with treatment control (not
placebo controlled) when we have an effective treatment. These are about as
good as it is assumed placebo effects figure the same in all tested treatment
groups.

------
erentz
This is practically ancient news at this point. RCTs are already underway in
China and now starting up in the US. The question that hasn't been well
answered anywhere is, assuming it does prove to work, can we make enough of
this stuff in the space of time to really make a difference? What would that
look like? Would we need to stop producing other drugs to switch over
production lines? Etc. What that would look like would be interesting to read
about.

~~~
whatshisface
Chloroquine is extremely common and can be bought in big bottles at your local
grocery store.

~~~
fspeech
Not in the US. Nobody makes it here. Over $250 per 12 tablets at Kaiser. HCQ
(hydroxychloroquine) is still used for autoimmune disease and is a lot
cheaper.

~~~
droithomme
Definitely. The State Department has a set of pages noting that mosquitoes
with malaria have developed chloroquine resistance in every country with
malaria, and recommends other drugs instead. The main manufacturer of
chloroquine, Bayer, stopped producing it a while back. Not sure who if anyone
even makes it these days. I'm assuming the Chinese trials are using some old
stock.

~~~
fspeech
They restarted old lines. These are not terribly hard to make. There was just
no demand.

~~~
droithomme
Do you know they (the Chinese presumably, if not who) restarted old lines, or
are you guessing that you think they did?

It would be great if chloroquinine is back in production.

~~~
fspeech
It was reported in the news. Also Bayer donated a bunch to China from their
stock in Pakistan. It's possible that HCQ, which is widely available, has
similar effectiveness.

~~~
droithomme
Thanks, that enabled me to find the 1/28 donation news:

[https://www.marketscreener.com/BAYER-AG-436063/news/Bayer-
to...](https://www.marketscreener.com/BAYER-AG-436063/news/Bayer-to-Donate-
Medicines-to-Treat-Coronavirus-29900181/)

It mentions "antibiotics and analgesics" but not quinine, but I'll accept
you've seen a more detailed report.

I was unable to find a report saying that Chloroquine lines have started back
up.

By HCQ do you mean Quinine Hydrochloride as is found in Tonic Water? Do you
have any links to studies showing it has "similar effectiveness" as
Chloroquine in treatment? I'm taking Quinine Hydrochloride at present since
it's harmless and available, but have not seen any studies about it
specifically regarding the new virus.

~~~
fspeech
HCQ is hydroxychloroquine, an antimalarial that is still widely available
because it is used for autoimmune diseases. It is a prescription only drug.
The antiviral property is described in this Lancet article:
[https://www.thelancet.com/journals/laninf/article/PIIS1473-3...](https://www.thelancet.com/journals/laninf/article/PIIS1473-3099\(03\)00806-5/fulltext)

~~~
droithomme
Thanks!

------
heavyset_go
Just a reminder that other antivirals like remdesivir that Gilead manufactures
retail for $2k for a 30-day supply in the US, despite costing roughly $40 in
other first world countries, and multiple US insurance companies needed to be
sued before they would cover them. To put this in perspective, transmission of
HIV could be virtually eliminated in the US if some of those antiviral drugs
were made available to at-risk populations.

Should there be a pandemic-level outbreak in the US, I just hope cost and IP
laws aren't the bottlenecks when it comes to preventing the spread of, and
recovery from, this disease.

~~~
ChickeNES
> To put this in perspective, transmission of HIV could be virtually
> eliminated in the US if some of those antiviral drugs were made available to
> at-risk populations.

No, the biggest issue with preventing HIV transmission is stigma of the
disease

Besides, Gilead, much like every other large pharmaceutical company, has
patient access programs to ensure that anyone who needs their medications can
get them: [https://www.gilead.com/purpose/medication-access/us-
patient-...](https://www.gilead.com/purpose/medication-access/us-patient-
access)

~~~
heavyset_go
> _Besides, Gilead, much like every other large pharmaceutical company, has
> patient access programs to ensure that anyone who needs their medications
> can get them_

Not if they're on Medicaid or Medicare[1], which _some_ providers through
those programs only very recently began to cover the medications due to
lawsuits against them.

Also, the co-pay coupon card only covers up to $7,200 in co-pays per year[1].

There is also the income gap where someone could make too much money to
qualify for their program, despite having no insurance, bad insurance or
catastrophic insurance plans. A contractor responsible for their own health
insurance might find themselves in that income gap.

And this program is at the discretion of Gilead, who can deny, change or
discontinue it at any moment.

[1] [https://www.truvada.com/how-to-get-truvada-for-
prep/truvada-...](https://www.truvada.com/how-to-get-truvada-for-prep/truvada-
cost)

------
fspeech
Hydroxychloroquine and chloroquine were successful in malaria prophylaxis on a
weekly dosing. Someone should start a trial among medical personnel to see if
it is effective in coronavirus prevention. These are non-specific antivirals.
Once virus takes hold, they have not yet been proven to be that effective in
clinical settings.

------
jstewartmobile
Why does astronomically priced remdesivir take precedence in most mentions
when, from the chart, chloroquine seems to have a similar inhibition rate, a
slightly lower cytotoxicity, and a much lower cost?

------
fspeech
Clinical trials for Remdesivir are ongoing.

There are some problems with the Chinese trials, which were the first to start
twenty days ago:

[https://clinicaltrials.gov/ct2/show/NCT04252664](https://clinicaltrials.gov/ct2/show/NCT04252664)

[https://clinicaltrials.gov/ct2/show/NCT04257656](https://clinicaltrials.gov/ct2/show/NCT04257656)

Trials were run in Wuhan by popular demand but the epicenter with a very over-
burdened medical system was probably not the best choice as trial site.
Recruitment of mild/moderate cases were particularly problematic because these
were not treated in hospitals in Wuhan at that time (you had to have a serious
enough case to have a real hospital bed). It is also hard to find patients who
have not tried other medication per the recruitment criteria.

The US organized trial
[https://clinicaltrials.gov/ct2/show/NCT04280705](https://clinicaltrials.gov/ct2/show/NCT04280705)
just started but is designed to be a lot more flexible and will show results a
lot sooner if Remdesivir is actually as effective as we all hope it to be.

~~~
koheripbal
The drug was also shown to be effective against SARS.

------
kingpiss
But didn't malaria develop chloroquine resistance in some areas? Whats
stopping sars-cov-2 from mutating like that?

~~~
jacquesm
I'd say we should cross that bridge when we get to it.

------
tim333
Chloroquine update - "Xu Nanping, vice minister of science and technology, at
a press conference in Beijing" Feb 21:

>Chloroquine Phosphate, which has been used for more than 70 years, has been
tested in 135 cases in Beijing and southern China's Guangdong Province. Among
them, 130 patients have light and common symptoms, and five are severe
patients.

>None of the patients with light and common symptoms have developed severe
symptoms. Four severe patients have been discharged from hospital, and one has
seen severe symptoms mitigated to normal, Xu said.
[http://www.china.org.cn/china/2020-02/22/content_75732846.ht...](http://www.china.org.cn/china/2020-02/22/content_75732846.htm)

which sounds promising.

------
MaupitiBlue
The guy in Washington was near death until Remdesivir was administered. He was
released a few days later.

Cool stuff.

------
jobseeker990
I'd love to understand the mechanism of action of chloroquine. Does the paper
touch on that?

~~~
rolph
[https://doi.org/10.1186/1743-422X-2-69](https://doi.org/10.1186/1743-422X-2-69)

>>We report, however, that chloroquine has strong antiviral effects on SARS-
CoV infection of primate cells. These inhibitory effects are observed when the
cells are treated with the drug either before or after exposure to the virus,
suggesting both prophylactic and therapeutic advantage. In addition to the
well-known functions of chloroquine such as elevations of endosomal pH, the
drug appears to interfere with terminal glycosylation of the cellular
receptor, angiotensin-converting enzyme 2. This may negatively influence the
virus-receptor binding and abrogate the infection, with further ramifications
by the elevation of vesicular pH, resulting in the inhibition of infection and
spread of SARS CoV at clinically admissible concentrations.

>>Chloroquine is known to block virus infection by increasing endosomal pH
required for virus/cell fusion, as well as interfering with the glycosylation
of cellular receptors of SARS-CoV

------
allovernow
This paper is a month old. I don't understand why this isn't common knowledge
yet.

------
jobseeker990
If this stuff is working, why haven't we seen the death rates start falling?

~~~
copperx
They have fallen these last days in China, if that means anything.

------
jjaredsimpson
I thought the name looked familiar. I'm not a doctor and I only googled for 10
minutes. I tore my achilles last year. I would never take this drug. I hope
I'm off base.

Wiki breadcrumbs

[https://en.wikipedia.org/wiki/Chloroquine](https://en.wikipedia.org/wiki/Chloroquine)

[https://en.wikipedia.org/wiki/4-Aminoquinoline](https://en.wikipedia.org/wiki/4-Aminoquinoline)

[https://en.wikipedia.org/wiki/Quinoline](https://en.wikipedia.org/wiki/Quinoline)

[https://en.wikipedia.org/wiki/Quinolone_antibiotic#Tendons](https://en.wikipedia.org/wiki/Quinolone_antibiotic#Tendons)

~~~
refurb
Chloroquine =/= quinolone class of antibiotics

