Rapid progress from Fast Grants

I was pleased to read this NYT reporting:

Yet another team has been trying to find drugs that work against coronavirus — and also to learn why they work.

The team, led by Nevan Krogan at the University of California, San Francisco, has focused on how the new coronavirus takes over our cells at the molecular level.

The researchers determined that the virus manipulates our cells by locking onto at least 332 of our own proteins. By manipulating those proteins, the virus gets our cells to make new viruses.

Dr. Krogan’s team found 69 drugs that target the same proteins in our cells the virus does. They published the list in a preprint last month, suggesting that some might prove effective against Covid-19…

It turned out that most of the 69 candidates did fail. But both in Paris and New York [where the drugs were shipped for testing], the researchers found that nine drugs drove the virus down.

“The things we’re finding are 10 to a hundred times more potent than remdesivir,” Dr. Krogan said. He and his colleagues published their findings Thursday in the journal Nature.

The Krogan team was an early recipient of Fast Grants, and you will find more detail about their work at the above NYT link.  Fast Grants is also supporting Patrick Hsu and his team at UC Berkeley:

And the work of the Addgene team:

Comments

Are you soliciting smaller donations for this or only big ones?

Minimum 10k, due to processing costs and staff constraints.

So much for being streamlined and without overhead.

Transparency in charitable donations exceeds perpedicular intrasivity when gonad insignificance is transcended in academia.

Thanks for your work. Would be nice if you could figure out a way to process small donations.

Imagine a go fund me type thing all this human creativity. Sure would love to feel like i contributed something to the fight here but 10k is not chump change for avg joes like me.

Got to pay your dues if you wanna cure the COVID blues
And you know it don't come easy
You don't have to shout or leap about
TC doesn't ask for much, he only wants your trust
And you know it don't come easy
Here within your reach
If you're rich enough to give it
Open up your heart, let's come together
Use a little love
And we will make it work out better

For $10,000 minimum .

Rally the boys
Ride paul ride

Rally the gals
Ride sally ride

Clench your fists
It’s time for a fight

By the sweat of your brow
Produce with might

Unite the clans
Rally the troops

Bloodied and battered
But still in the fight

Rally the nerds
Rally the rich

Rally the infirmed
Rally the fit

Awaken... oh sleeping giant
Awaken from your slumber

It’s time for a rally
To arms, to arms, tonight!

Roll up your sleeves
Batten down the hatches

Harden your nerves
Throw in the reserves

Backs are to the river
Forward we must go

Rally gentlemen... rally
Ladies form up your legions

It’s time for a fight!

Bring the big brains
Let’s make some gains

Rally people, rally
Make ready for the second surge

Watch, some fast grant recipient will produce the first safe and effective vaccine and prior's head will simultaneously explode.

Did someone forget to mention that with Krogan, there is already an institute able to work nimbly since 1979? - "Gladstone is home to four major institutes, each representing different yet interconnected areas of focus. Investigators have the freedom to follow their research wherever it leads, and work closely with their colleagues in all institutes to deeply probe important questions in biomedicine. Above all, they champion highly interactive, creative, and innovative approaches to science as they seek prevention, treatments, and cures for major diseases."e https://gladstone.org/science/institutes

They have even been around much longer than Emergent Ventures Fast Grants, though the mission statement is similar - "Gladstone is an independent, nonprofit life science research organization located in the epicenter of biomedical and technological innovation in the San Francisco Bay Area. Gladstone has created a research model that disrupts how science is done, funds big ideas, and attracts the brightest minds."

I agree with the Fast Grants approach and concept: the more researchers looking at the virus from many different angles the more likely a breakthrough. But I've wondered whether researchers are resistant to collaboration, fearful that others might steal their ideas or research, or take credit for their findings. Based on this blog post my concerns seem unfounded. Again, I believe there's more likely to be a breakthrough with researchers going their separate ways, but at some point collaboration will accelerate us to the goal of developing a vaccine. Does Fast Grants have anything built-in the grants that would facilitate/promote collaboration?

What are the odds anyone will figure out how to compress the decades of research in coronavirus biology and vaccine strategies into 3-6 months?

What I find bizarre is the statement "no vaccines has been developed in less than four years" while ignoring the five decades plus of work on coronavirus vaccines, which include a number of commercial coronavirus vaccines for farm animals, plus SARS and MERS vaccines which were ready for human trials circa 2015, and in human trials in 2019, respectfully.

(MERS-CoV vaccine shows promise in phase 1 trial
Modjarrad K, et al. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30266-X.
Yoon I, Kim JH. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30397-4.

August 5, 2019
Data from a phase 1, open-label, single-arm, dose-escalation trial demonstrated the tolerability, safety and immunogenicity of a vaccine against Middle Eastern respiratory syndrome coronavirus, or MERS-CoV, researchers reported.)

The SARS-Cov2 vaccines are modifications of existing SARS and MERS vaccine work.

Work that was funded more than a decade ago building on new research built on the human genome project massive funding which advanced gene sequencing at least a thousand times. There was massive funding to pay more workers to build the capability to create and then manufacture vaccines in the US.

Conservatives, however oppose paying workers.

Fast Grants is an attempt by economists to figure out how to get the benefits of paying lots of workers for decades without paying any workers to work, and get the same results in a few months.

The work on SARS was mostly dropped when the virus faded out... I was at Mayo when we chucked the SARS vials into the freezer and forgot about them. Agree that attention span is necessary, but if you think that it exists you don't work in research ;)

'What I find bizarre is the statement "no vaccines has been developed in less than four years" while ignoring the five decades plus of work on coronavirus vaccines'

Right, it's as silly as Patrick Collison's claim that innovation was so much faster decades ago, when Apollo 8 took only 134 days to launch: "On August 9 1968, NASA decided that Apollo 8 should go to the moon. It launched on December 21 1968, 134 days later".

I guess the years it took to build and launch Apollo 1-7 don't count. By that way of thinking, it took only seconds to launch Apollo 8: "10, 9, 8 ... lift-off!".

This paper and one from a group mainly at Scripps and Mt. Sinai were the two best AI drug repurposing papers I've read over the last two months. Unfortunately, few if any of these compounds are making their way into clinical trials. So much time and effort is being wasted and it's likely that a drug that actually works is going to be left behind.

"“The things we’re finding are 10 to a hundred times more potent than remdesivir,” Dr. Krogan said.

Yes, but are the FDA approved.

Some of them are: , haloperidol and melperone, which are used to treat schizophrenia, Two antihistamines, clemastine and cloperastine, the hormone progesterone.
I am not sure about the agonist sigma 2 receptor PB28 which they claim had the largest effect

going to order some PB28 and see if it cleans my fish tank https://www.tocris.com/products/pb-28-dihydrochloride_2562

Have you used PB 28 dihydrochloride?
Submit a review and receive an Amazon gift card.

it would appear so

"Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo"

I don't see PB-28 ( cyclohexylpiperazine) in that paper

"The things we’re finding are 10 to a hundred times more potent than remdesivir,” Dr. Krogan said. He and his colleagues published their findings Thursday in the journal Nature."

From Dr Krogan's mouth to God's ears, but really what are the chances he is correct?

Because of our stupid tax laws, I give all my charity in alternating years and this is an off year. I hate bad laws.

These drugs are potent in vitro against a line of cells. Whether they will do well in vivo needs to be proven. We have seen for example that hydroxychloroquine which is on their list has no proven efficacy in clinical studies.
Still it’s a good list to keep investigating. It’s doing the work needed to get there.

I'd gladly donate my stimulus check but Trump and Mnuchin are very slow at sending them out.

FWIW, mine has gone from indeterminate state to pending.

Wrex is still my favorite Krogan.

there are reportedly some intriguing results for Vitamin D... unfortunate that more data is not being gathered for supplements such as zinc, given that millions are taking zinc and some medical professionals are prescribing it

I am glad to see
That Someone
At least
Is funding
Public research.

Funny how we starve
Publicly funded research
And then
Pass the hat when
There are signs of success.

Starve the beast. stick around for the feast - 10,000 dollars at the door.

Good to see Addgene get some support.

LA Times today picked up on Dr. Brenner's paper on nicotinamide riboside vs. SARS-CoV-2... I don't understand why you and your enormous staff haven't! (Anyway, check it out, it's important:
https://www.biorxiv.org/content/10.1101/2020.04.17.047480v2

Scientists working for the US military have designed a new Covid-19 test that could potentially identify carriers before they become infectious and spread the disease, the Guardian has learned.

In what could be a significant breakthrough, project coordinators hope the blood-based test will be able to detect the virus’s presence as early as 24 hours after infection – before people show symptoms and several days before a carrier is considered capable of spreading it to other people. That is also around four days before current tests can detect the virus.

The test has emerged from a project set up by the US military’s Defense Advanced Research Projects Agency (Darpa) aimed at rapid diagnosis of germ or chemical warfare poisoning. It was hurriedly repurposed when the pandemic broke out and the new test is expected to be put forward for emergency use approval (EUA) by the US Food and Drug Administration (FDA) within a week.

Well done, which I hear is better than well said.

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