
COVID-19 Therapeutics Accelerator - sandGorgon
https://www.gatesfoundation.org/TheOptimist/Articles/coronavirus-mark-suzman-therapeutics
======
philipn
Edit: contact made, thank you!

If anyone is reading this with connections to the Gates Foundation: Please
contact Dr. Robert Kruse at John Hopkins.
[https://twitter.com/RobertLKruse](https://twitter.com/RobertLKruse). I have
been trying to get in touch with people at Gates. This announcement
unfortunately features no contact email address :(

Dr. Kruse is developing an extremely promising therapeutic, ACE2-fc, which
will both neutralize the virus and treat the symptoms of the disease. It has
been shown to work in vitro; variants have been tested in animals models; and
its been through Phase II human trials for a different indication. A variant
of the therapy, soluble ACE2, is being trialed in humans now in China.

Details on the approach can be found in his paper here:

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029759/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029759/)
see "ACE2 immunoadhesin strategy"

~~~
pkaye
For you know if the ACE2 genes mentioned with relation to coronavirus have
anything to do with ACE inhibitors and ARB inhibitors?

~~~
delhanty
This may be relevant: there's a recent (3rd March) _hypothesis_ due to Rami
Sommerstein from Department of Infectious Diseases, Bern University Hospital
[0] that ACE inhibitors are a potential _risk factor_ for fatal Covid-19 in
those patients taking ACE inhibitors for hypertension/diabetes/cardiovascular
disease:

>The largest Chinese study with 44,672 confirmed cases of Covid-19 shows a
high overall case fatality rate (CFR) of 2.3% [2]. Important co-morbidities
are hypertension (CFR 6.0%), diabetes (CFR 7.3%), cardiovascular disease (CFR
10.5%) and age >70 (CFR 10.2%) [2]. Similar co-morbidities were noted for the
SARS outbreak in 2003.

> ...

>On the one hand, it has been shown that the Covid-19 agent (also known as
SARS-CoV-2), uses the SARS-COV receptor angiotensin converting enzyme (ACE) 2
for entry into target cells [4]. The interface between ACE2 and the viral
spike protein SARS-S has been elucidated and the efficiency of ACE2 usage was
found to be a key determinant of SARS-CoV transmissibility [4].

>

>On the other hand, it could be shown in animal experiments that both the ACE-
inhibitor lisinopril and the angiotensin-receptor blocker losartan can
significantly increase mRNA expression of cardiac ACE2 (5-fold and 3-fold,
respectively) [5]. Further, losartan also significantly increases cardiac ACE2
activity [5].

Edit: thank you philipn for your twitter link.

[0]
[https://www.bmj.com/content/368/bmj.m810/rr-2](https://www.bmj.com/content/368/bmj.m810/rr-2)

~~~
philipn
Please see my twitter account for lots on this. I'm in contact with a bunch of
top researchers on this topic (renin-angiotensin system; ACE2/Ang 1-7/Mas
axis; ARB usage for viral diseases) and will be posting a summary update soon:

[https://twitter.com/__philipn__/status/1235756671852589056](https://twitter.com/__philipn__/status/1235756671852589056)

It may be the other way around: ACEi/ARB may be protective. HTN without
ACEi/ARB would be non-protective, potentially so much so that it skews the
group fatality numbers. This is because people with HTN have a different
renin-angiotensin system profile: more AT1R, less AT2R, more ACE, potentially
less ACE2.

This is being looked at now. But the key is that in every study ever done on
viral lung disease, etc, AT1R blockade was highly beneficial, and we know that
ACE2-knockout basically screws up lungs, makes viral lung disease way worse,
etc. Please see my twitter posts.

The virus eats up ACE2, downregulating it as it binds. This would have
delirious effects. Check out the linked "essential reading" twitter post.

Will be posting a summary to my twitter soon.

~~~
Alex3917
A few days ago I started taking a low dose of an OTC ACE inhibitor in order to
upregulate my ACE2 receptors. This is what the literature that was written
before the current epidemic about surviving novel Coronavirus pandemics says
to do, and the new evidence that comes out each day is actually validating
this strategy.

It's only the scientists who didn't start studying Coronaviruses until two
weeks ago who seem to think that having ACE2 receptors is dangerous.

~~~
refurb
If the virus is infecting a cell through the ACE2 receptor, wouldn’t
upregulating the receptor just increase the risk of infection?

As per the paper, you want to either block the receptor or down regulate it.

~~~
Alex3917
That definitely could be true, but from what I've read it probably isn't. One
of the ways the virus kills people is by destroying their ACE2 receptors,
which your lung cells need to function. If you blocked them all, your lung
cells would die anyway. So as long as the virus can enter your lung cells, you
might as well prevent it from killing them by making extra ACE2 receptors.
That's the theory anyway.

There are also many other ways you can block the virus from entering your
lungs that don't involve downregulating your ACE2 receptors.

------
JonathanFly
The Gates Foundation was on this early:

[https://www.gatesfoundation.org/Media-Center/Press-
Releases/...](https://www.gatesfoundation.org/Media-Center/Press-
Releases/2020/01/Gates-Foundation-Commits-10-Million-to-Global-Response-
to-2019-nCOV)

[https://www.gatesfoundation.org/Media-Center/Press-
Releases/...](https://www.gatesfoundation.org/Media-Center/Press-
Releases/2020/02/Bill-and-Melinda-Gates-Foundation-Dedicates-Additional-
Funding-to-the-Novel-Coronavirus-Response)

>The foundation will provide up to $100 million to improve detection,
isolation and treatment efforts; protect at-risk populations in Africa and
South Asia; and accelerate the development of vaccines, drugs and diagnostics.

That early investment is going to be so valuable. It's not so easy to get
those six weeks back by spending 10x the amount the later.

------
aazaa
I'm seeing a lot of unwarranted conclusions in this thread. In vitro work
usually goes fast in drug development. The painfully slow process is human
testing.

The article says nothing about shortening the time from in vitro discovery to
first use in humans. As far as I can tell, it just promises $125 million for
early stage work. That's a lot of money, but a drop in the bucket by drug
development standards.

Good to know the effort is being made, just keep some perspective.

~~~
zerkten
Part of the problem is that most people know very little about how drugs are
developed, but they form a type of connection because they know the Gates
Foundation. My hope is people gain a deeper appreciation of what's involved
across many of these threads, but I feel like the opportunity will be missed.

------
narrator
How about confirming that Chloroquine works?[1] Yeah, it's a boring old out of
patent drug. New uses for out of patent synthetic drugs is like the most
unsexy thing in all of medicine. Even herbal cures get more respect, because
they are from mother earth.

[1][https://www.sciencedirect.com/science/article/pii/S016635422...](https://www.sciencedirect.com/science/article/pii/S0166354220301145)

~~~
jmnicolas
This makes no sense to me : malaria is due to a bacteria and COVID19 is a
virus, why choloroquine would work on both ?

~~~
Cantbekhan
Several EU countries in addition to China are already actively using
chloroquine and hydroxichloroquine to treat COVID19 patients. And I mean
outside trials.

For instance:

Here are the Netherlands treatment guidelines (in Dutch):
[https://lci.rivm.nl/covid-19/bijlage/medicamenteuze-
behandel...](https://lci.rivm.nl/covid-19/bijlage/medicamenteuze-
behandelopties)

Here are the Italy treatment guidelines (in Italian):
[http://www.simit.org/medias/1555-covid19-linee-guida-
trattam...](http://www.simit.org/medias/1555-covid19-linee-guida-
trattamento-01mar.pdf)

I think the anecdote on how they found out about the effectiveness of
chloroquine in China is fascinating and has nothing to do with the in vitro
efficiency study nor with the malaria usage but solely with the
immunomodulator effect. They just noticed that there were no lupus patients
infected with Covid19. And after investigating with the dermatology dept, they
confirmed that indeed there were no reported lupus patients of that hospital
infected with covid19.

Their common treatment was chloroquine...

Source:
[https://www.jqknews.com/news/388543-The_novel_coronavirus_pn...](https://www.jqknews.com/news/388543-The_novel_coronavirus_pneumonia_has_short_term_curative_effect_on_the_treatment_of_new_crown_pneumonia.html)

It should be noted that as far as the Chinese are concerned, it doesn't seem
like there is any debate about chloroquine usefulness for COVID19.

Sources:

[https://pubmed.ncbi.nlm.nih.gov/32075365-expert-consensus-
on...](https://pubmed.ncbi.nlm.nih.gov/32075365-expert-consensus-on-
chloroquine-phosphate-for-the-treatment-of-novel-coronavirus-pneumonia/)

and [https://pubmed.ncbi.nlm.nih.gov/32074550-breakthrough-
chloro...](https://pubmed.ncbi.nlm.nih.gov/32074550-breakthrough-chloroquine-
phosphate-has-shown-apparent-efficacy-in-treatment-of-covid-19-associated-
pneumonia-in-clinical-studies/)

~~~
gnulinux
Why do these things take slowly in US but are much faster in the EU? Even
though Italy and Netherlands are already using it, no patient in US is treated
with chloroquine since it's not FDA approved. Why does FDA approval matter for
a brand new disease, in an emergency situation like this?

~~~
zerkten
It doesn't for many known medications. But, it's a factor for new and less
well understood medications.

There is "on label" and "off label" usage of drugs. Just because this existing
medication is being used in the EU, or has made its way into guidelines, does
not mean that it would even make it through EU approvals. It's being used "off
label" if it's used for a new condition.

I've personally been treated "off label" for a condition using a drug
developed and FDA approved for a serious condition that you wouldn't
immediately associate with my condition. It was weird being unable to find any
substantive literature on that medication and my condition, but that's the
nature of uncommon conditions, or being at the edge like we are with COVID-19.

US doctors will, based on the evidence available, make their own decision on
whether to follow the treatments used by their colleagues in the EU and China.
They are not going to be held up by FDA approval for off-label use, but they
may find things that warrant FDA review and approval because they feel the
outcome is not worth the risk. The impact on the US is trailing China and EU
to some degree. This buys a little time for some very smart people to do some
level of analyses of what's happening elsewhere. It'd be a little different if
the early waves hit here first.

~~~
gnulinux
So a US doctor doesn't need FDA approval to be able to prescribe something
like chloroquine or Remdesivir for a COVID19 patient as long as they believe
it'll be helpful to patient, did I understand it correctly?

~~~
zerkten
Yes, but in practice it is rarely the situation where a doctor is making this
call on their own. The hierarchy from doctor to senior leadership should be
involved in decisions like this because there are many more ramifications than
just one patient.

From the doctor's perspective, at minimum this is a cover-your-ass move
because they don't want to get blamed for an adverse event. The administration
needs to manage the risk too, and find other experts to review the situation.
They may also need to manage supplies, or costs. This is really no different
from the usual medical bureaucracy in the US.

One item that I'll end with is that approval processes (FDA, EU, etc.) provide
no guarantees. There are many drugs that have been approved and then removed
from general use based on additional experience, or long-term clinical trials.
It's obviously good to do more trials and get approvals, but patients and
doctors really want the best possible outcome given the situation.

------
chrstphrhrt
Great to see people rallying around possible solutions and spreading the info.

Personal anecdote, I was looking up whether to stop occasional cannabis usage
as a precaution for a while because it has been labelled an immunosuppressant
and an immunomodulator. I don't understand enough of the science to decide, so
I'm stopping, but what I saw in those papers suggested that it is good at
preventing autoimmune diseases from getting out of hand. Any expert
knowledge/opinion very welcome, as many people have access to this drug
already.

~~~
bionhoward
The biggest problem about cannabis re: covid19 is if you smoke it, it’s gonna
impair the cilia which help clean out your lungs, also you’re putting your
lips on some dirty piece (especially bad if shared between multiple people as
one person being exposed equals everyone else sharing the piece gets exposed)

Definitely avoid combustion with shared bongs. If we might get sick with
something that’s gonna impair our lungs, we ought to take action to increase
lung function e.g. VO2Max (lactate threshold training / HIIT / Lung muscle
exercises with incentive spirometers OR IMST devices) Not sure about the viral
implications of systems biology of immune effects of cannabis, but it’s an
interesting topic

------
jokowueu
"The proposal is a biologic that blocks 2019-nCoV entry using a soluble
version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused
to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody
with maximal breath to avoid any viral escape, while also helping to recruit
the immune system to build lasting immunity. The ACE2-Fc therapy would also
supplement decreased ACE2 levels in the lungs during infection, thereby
directly treating acute respiratory distress pathophysiology as a third
mechanism of action."

------
notaharvardmba
EIDD-2801 from DRIVE/Emory University is also looking extremely promising.
[https://www.ncbi.nlm.nih.gov/pubmed/31578288](https://www.ncbi.nlm.nih.gov/pubmed/31578288)
They have a GoFundMe also to I guess try to get things ramped up:
[https://charity.gofundme.com/o/en/campaign/end-pandemics-
now](https://charity.gofundme.com/o/en/campaign/end-pandemics-now)

~~~
nopinsight
This needs to be its own post and shared as much as possible.

The above may yield a pill that patients can take at home, reducing further
spread of infections that can easily occur in clinical settings. Without such
a pill, hospital overflow will occur in any area with more than a few thousand
cases. And there will be 100s-1000s of cities worldwide that medical resources
could be overwhelmed within a few months.

We need to explore all avenues now. In only 3-4 months, there will be 100,000s
of deaths worldwide, if an effective treatment that can be administered
outside of hospital settings is not available.

~~~
nopinsight
For those who disagree, please study the coronavirus growth rate when no
serious containment measure is implemented then try to provide evidence to the
contrary (ie, either containment measures will be sufficient in most
countries, or that my predictions above are flawed somehow.)

A scientist recently presented at the AHA meeting with these bullet points:

“- 4.8 million hospitalizations associated with the novel coronavirus

\- 96 million cases overall in the US

\- 480,000 deaths

\- Overall, the slide points out that hospitals should prepare for an impact
to the system that's 10 times a severe flu season.”

The figures are just for the US, not the world.

[https://www.businessinsider.com/presentation-us-hospitals-
pr...](https://www.businessinsider.com/presentation-us-hospitals-preparing-
for-millions-of-hospitalizations-2020-3)

------
GreaterFool
Does one acquire immunity after going through CoV infection? What about
SARS/MERS?

If I understand correctly there are many strains of influenza and they mutate.
That's why new vaccines are needed.

What about SARS/MERS? Did they mutate too?

~~~
SonOfLilit
Not a doctor or biologist.

From my understanding (I.e. someone who wasn't a doctor or biologist once told
me), the flu virus is special in that it is very big for a virus and has
something akin to primitive sexual reproduction: it is made of six(?) parts
and if two strains of flu infect the same cell, the cell will give birth to
viruses that have each part chosen at random from one of the two strains (e.g.
aBCdEF or AbcdEf etc').

That's why there are so many strains of flu and the vaccine changes every
year.

Apart from that, every virus mutates, and from what I've read there are
already at least two known functionally different strains of nCov-2019 (one
more aggressive than the other). However, I'd wager the same vaccines and
medicines would work for both - to get resistance you need selection pressure
or the amount of variance you get from sexual reproduction.

Edit: oh, and nCov-2019 attacks the immune system in a way that seems to lower
or prevent acquiring immunity from reinfection.

~~~
sudosysgen
There is no reason to believe that SARS-CoV-2 attacks the immune system.

The study that suggested ADE for this virus showed a very mild effect in
vitro. However, antibodies still prevented infection. More crucially yet, a
high number of viruses exhibit ADE in vitro, yet only two exhibit ADE in vivo.
Moreover, even in vitro, infection of immune cells by the virus did not lead
to viral replication. It's therefore unlikely that it shows ADE in humans,
especially since its far less severe than viruses that do.

You might notice that for critical cases, lymphocytes counts are down. The
issue is that lymphocyte counts are low, yet those patients show very high
cytokine levels, and lymphocytes also exhibit exhaustion. Studies in a
clinical setting have shown that indeed cytokine levels are a good predictor
of lower lymphocyte counts. Thus this seems better explained by the cytokine
storm.

Another thing that's good to know is that this coronavirus seems to have a
very good exoribonuclease, which is an error checking enzyme. Mutation rates
are also quite low, empirically. It is thus probable that this virus will not
evolve too much.

Finally, the study that suggests that there are two lineages is deeply flawed.
When you take into account the founder effect of international dissemination
right before border controls are implemented, and the low mutation rate, you
will find that the observation that led to the conclusions that there are two
strains is not significantly more likely than the null hypothesis that this is
simply a coincidence. Therefore it is not possible to make conclusions about
the existence of strains, and certainly not possible to suggest they would
behave differently in any way.

~~~
SonOfLilit
Awesome, learned a bunch of things, thanks!

(One of which was that biologists have a more specific definition of "virus
attacks X system" than computer security researchers, so my wording seems to
have been off there. I was trying to say "seems to do something against its
effectiveness, because we see cases of reinfection after a short time")

------
christkv
This study looks interesting [https://pharmaphorum.com/news/china-backs-
roches-actemra-to-...](https://pharmaphorum.com/news/china-backs-roches-
actemra-to-fight-coronavirus-complications/)

Actemra is a biologic approved in 2010 in the US for rheumatoid arthritis and
tones down immune responses by inhibiting interleukin 6 (IL-6).

Basically it turns down the effect called a cytokine storm which causes your
own immune system to attack your lungs. This kills a lot of people.

Also take Vitamin D3 (1000 IU a day) it's proven to help lessen respiratory
illness if you catch the virus.

------
epmaybe
While low yield, it would be interesting to look at fast-tracked whole genome
data from infected patients, and see if there are any SNPs or mutations that
could put you at higher risk for mortality.

------
dorfsmay
I imagine they are already in contact, given they are in the same state, but
just in case:

[https://www.chulab.org/announcements](https://www.chulab.org/announcements)

[https://twitter.com/HelenChuMD/status/1235339042889359361](https://twitter.com/HelenChuMD/status/1235339042889359361)

------
known
Combination lopinavir and ritonavir is used to treat COVID-19 in
India/Thailand [https://www.telegraphindia.com/health/anti-hiv-drugs-
given-t...](https://www.telegraphindia.com/health/anti-hiv-drugs-given-to-
coronavirus-affected-elderly-italian-couple-in-jaipur/cid/1752505)

------
dreichel
Can someone please explain if I am currently taking Losartan should I switch
to something else? I keep reading conflicting articles. Some say it could be a
benefit and actually used in treatment of covid 19. But other articles are
saying the opposite. Thank you.

------
dreichel
Can someone please weigh in and say if someone who takes Losartan should
switch to something else at this time? I am currently on that med and I am
panicking after reading several articles. Thank you.

------
mothsonasloth
Funding and government initiatives aside, is there any tech platforms that
facilitate scientific collaboration?

It mostly seems to be just dropbox equivalents that let you drag and drop test
results and PDFs into shareable folders.

~~~
dredmorbius
WWW:
[http://info.cern.ch/hypertext/WWW/TheProject.html](http://info.cern.ch/hypertext/WWW/TheProject.html)

Though specific discussion of essential useful features and shortcomings of
the basic concept might be helpful.

------
classics2
Won’t every person on earth in contact with other humans already be either
immune by exposure or dead within 6 months?

------
victor106
> And in 2017, the Coalition for Epidemic Preparedness Innovations (CEPI) was
> created with nearly $650 million from Germany, Japan, Norway, Wellcome, and
> our foundation. Since then, others have come on board, including the UK,
> Canada, Ethiopia, Australia, Belgium, and the European Commission, to
> dramatically reduce the time it takes to develop vaccines for emerging
> epidemics, and ensure they are accessible, available, and affordable.

Such a shame that the US is not on that list of countries.

------
jonnycomputer
remdesivir

[https://angrybearblog.com/2020/03/novel-coronavirus-and-
bett...](https://angrybearblog.com/2020/03/novel-coronavirus-and-better-
unsafe-than-sorry.html)

------
b34r
“ Epidemics introduce a paradox to the world. Viruses like COVID-19 spread
rapidly but developing vaccines and treatments to stop them moves slowly.”

That’s not what a paradox is... sigh.

~~~
farseer
Don't know why you are being down voted. This is hard scientific and economic
reality, not a paradox.

~~~
hellllllllooo
Because it's irrelevant pedantry?

~~~
pasquinelli
Yeah, but irrelevant pedentry doesn't always get downvotes.

------
lqet
Meanwhile, doctors in Germany begin to build their own protective suits
because professional ones are hard to get:

[https://ais.badische-
zeitung.de/piece/0a/f1/b2/8f/183612047-...](https://ais.badische-
zeitung.de/piece/0a/f1/b2/8f/183612047-h-720.jpg)

[https://ais.badische-
zeitung.de/piece/0a/f1/b2/8a/183612042-...](https://ais.badische-
zeitung.de/piece/0a/f1/b2/8a/183612042-h-720.jpg)

~~~
hef19898
Proof _one_ doctor build his own PTE suit. No proof they aren't available per
se.

------
avocado4
CDC should require every lab and hospital screening for COVID19 to send lung
CT and lab data to the government, and release it as a public dataset for AI
developers to build screening models.

~~~
pishpash
CDC too slow, non-reviewed papers already out:

[https://arxiv.org/pdf/2002.09334.pdf](https://arxiv.org/pdf/2002.09334.pdf)

[https://www.medrxiv.org/content/10.1101/2020.02.25.20021568v...](https://www.medrxiv.org/content/10.1101/2020.02.25.20021568v2)

~~~
hef19898
Non-reviewed being the key here.

------
tus88
Good news.

------
SonOfLilit
Please fund clinical trials of zinc as COVID cure/statistical preventative:

[https://slatestarcodex.com/2020/03/02/coronavirus-links-
spec...](https://slatestarcodex.com/2020/03/02/coronavirus-links-speculation-
open-thread/#comment-859920)

------
saadalem
So I have a weird hobby of reading case studies, and today my curiosity lead
me to wonder why colonoscopy doctors do not use UVC...

(UVC is a specific wavelength of light of the UV band - think UV lights in
clubs - it kills bacteria and is now used in hospitals to sterilize equipment
) ...to cleanse the colon of both good and bad bacteria in the intestines in
order to immediately cure patients with IBS (Irritable Bowel Syndrome) and
Chrons, which are both caused by harmful gut bacteria that even the best
probiotics unfortunately do not successfully treat. (Which lead me down the
rabbit hole...) If you want to be as sick to your stomach as I am, here is the
truth and I am happy to source over 8 case studies out of dozens on the
subject which all say the same thing, UVC kills cancer cells as well as
COVID-19 and also strong ionized oxygen can kill any virus on contact
instantly. Those tiny tentacles of Covid 19 virus will be neutralized in a
fraction of a second in contact with the ionized oxygen.

~~~
objclxt
> UVC kills cancer cells as well as COVID-19

It kills _any_ cell, it's not discriminatory. Oh, and UV-C is carcinogenic.
Once you understand that you might appreciate why we don't just shove a UV
light up a colon.

~~~
javajosh
Well, everything is carcinogenic. Given that sunlight has plenty of UV-C, it's
probably okay to expose tissues to it briefly. (Of course, this is one of
those treatments that definitely needs careful study.)

~~~
russholmes
UV-C is completely absorbed by atmospheric oxygen and ozone - none reaches the
ground.

