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Coronavirus Spike Protein Binder Design

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Re: Coronavirus Spike Protein Binder Design

#41

There is already stuff like this out there: https://www.biorxiv.org/content/10.1101/2020.02.01.929976v2.... Also, it appears as though convalescence therapy is working (i.e., treating people with the plasma from recovered patients) https://www.straitstimes.com/asia/east-asia/china-seeks-plas... https://news.yahoo.com/chinese-doctors-using-plasma-therapy-...

Why cant they just extract the protein from the coronavirus?

They can and are working on it/have already done it. The key then is to make it in large quantities. One way to avoid needing to make the protein is to deliver mRNAs for the heavy chain and light chain of the antibody. This would be faster, but it is not a proven technology so it's unlikely to work anytime soon (<1y) so convalescence treatment is much easier to do since blood transfusions are super common and well established.

Re: Coronavirus Spike Protein Binder Design

#42
post #23

Earlier quoted context omitted.

Public health systems, well-funded or not, are not a cure-all. I'd be curious to hear if you have any examples - if anything, they are reliant on research funded by the huge amount of money sloshing around the US healthcare system. Given a fixed annual budget, a public health system essentially has to decide what "healthy" or "cured" means, and set some quality of life to cost of treatment ratio. Some examples: my da…

I’m sorry to hear about your wife’s friend. But both examples you gave (people having to fight for further diagnoses of outside-case health problems) are really common with private healthcare in the United States too - we’ve just shifted the burden of cost of treatment/quality of life decisions to private entities who typically are only interested in furthering shareholder value. To give a personal anecdote as well:…

> I’m sorry to hear about your wife’s friend. But both examples you gave (people having to fight for further diagnoses of outside-case health problems) are really common with private healthcare in the United States too - we’ve just shifted the burden of cost of treatment/quality of life decisions to private entities who typically are only interested in furthering shareholder value.

Having a profit motive is only a serious problem when there is insufficient competition. Otherwise companies that try to make outlandish profits would lose business to companies that offer better coverage for lower premiums by taking smaller profits. Insurance company profits are only a single digit percentage of US healthcare costs; eliminating them wouldn't make a real dent anyway. (In many cases the "profits" are also unavoidable. For example, if the insurance carrier owns its building then the internal rents are "profit" but if you want to replace them you would still need a building and then have to pay for it from somewhere else. Every dollar you spend on anything is profit to somebody.)

And a profit motive will in general tend to lower costs, because a company that can eliminate waste and then charge lower premiums for the same coverage will get more business and make more money. There are a lot of reasons it doesn't work out that way for US health insurance, e.g. when it's provided with employer subsidies under tax incentives it reduces competitive pressure (employees can't choose another insurer) and the tax incentives reduce price sensitivity. But a big one is this:

> I would like to understand if the world really does rely on US private-healthcare funded research - I’ve heard this argument mentioned before and have always been curious about it.

The basis premise behind the patent system is like this. It takes a lot of money to do R&D and it may not even turn into anything, but once it's public knowledge, everybody starts making the thing and not just the party who paid for the R&D. Which makes it a lot more profitable to wait for somebody else to do R&D and then go into competition with them than to do the R&D yourself, so then nobody has the incentive to do it. Patents say if you do the work you get a temporary monopoly on selling the thing to give you some time to recover your R&D before competition drives down the price.

In principle this allows the market to set the price. If you invent a more efficient light bulb, you can ask $1000 for one but no one will pay that much even if you have a monopoly, they'll just buy the old light bulbs. But you might be able to charge as much of a premium as your light bulb will save in electricity over the existing ones and still find buyers.

With drugs the incremental value is often very high -- it could save your life when the alternative is that you die. Which is what you want to happen, because you want a large financial incentive to do R&D that can save lives. But then the cost can be really high which makes people want some kind of insurance.

When you have private insurers in competition with one another, you still basically have a market. If the drug maker demands a trillion dollars to treat one patient, any insurance company willing to pay that would have to charge premiums nobody can afford, and then nobody would buy that insurance and the drug maker would get no sales. So there is a limit on what they can charge, but it's still pretty high, because people really want their insurance to cover those drugs and will strongly prefer insurance carriers that do over those that don't. And then you get the large financial incentive to do life-saving R&D as desired.

With a single payer system, that competition between insurers doesn't exist. If the system refuses to pay the maker's price for a drug, the system can't lose customers to a competing insurer that will. Which means you have a monopsony buyer that can dictate prices. Naturally they have the incentive to dictate prices that are lower. But higher prices during the exclusivity period is how the patent system directs money to R&D. By dictating lower prices they're not paying their share of the cost of developing the drugs that only exist because the US is paying more, and causing some life-saving drugs to not exist because the US market on its own isn't enough to justify the R&D.

Re: Coronavirus Spike Protein Binder Design

#43

Earlier quoted context omitted.

Why cant they just extract the protein from the coronavirus?

They can and are working on it/have already done it. The key then is to make it in large quantities. One way to avoid needing to make the protein is to deliver mRNAs for the heavy chain and light chain of the antibody. This would be faster, but it is not a proven technology so it's unlikely to work anytime soon (<1y) so convalescence treatment is much easier to do since blood transfusions are super common and well es…

did they not have the same problem in doing the aids vaccine?

Re: Coronavirus Spike Protein Binder Design

#44

This is what antibodies do, right? How exactly does the body figure out how to configure the variable part of the antibody so that it binds? Does it just try countless variations until it finds a match? Can we take an antibody from a healed person and reverse engineer the binding protein?

> How exactly does the body figure out how to configure the variable part of the antibody so that it binds? Does it just try countless variations until it finds a match?

Not a biologist but IIRC, the body produces cells with a shuffled sequence of DNA. Then this specific cell produces one specific variant of antibodies, located on its surface. At this point the antibody is just a random sequence that matches with nothing.

If one day a virus (or anything else) happen to match with the antibody located on the surface of the cell, the cell will then multiply and most of the new cells will specialize into antibody-producing cells (released in the body, not remaining on the surface of the cell) and a small amount will not. The one who aren't producing antibodies are kept in the body for a long time, and they are here to provide quick specific response next time you meet the pathogen again (that's where immunity comes from).

So yeah, it's basically brute-force until a matching antibody is found.

Re: Coronavirus Spike Protein Binder Design

#45
post #38
post #6

If you find a protein that blocks the virus, how difficult would it be to find a drug delivery mechanism that is capable of reaching all the important cells?

Typically such a protein would be delivered via infusion (IV), I believe.

the main trophic target of this virus is lung tissue. a nebulizer would deliver the mRNA-Fc complex to the lung tissue.

the other way around would look a lot like a classic vaccine delivered by injection, and encapsulate the mRNA into a vesicle that targets antigen presenting cells in the lymphatic system which then presents the mRNA product as an antigen-MHC complex to specify what antibody to generate.

Re: Coronavirus Spike Protein Binder Design

#46

Earlier quoted context omitted.

They can and are working on it/have already done it. The key then is to make it in large quantities. One way to avoid needing to make the protein is to deliver mRNAs for the heavy chain and light chain of the antibody. This would be faster, but it is not a proven technology so it's unlikely to work anytime soon (<1y) so convalescence treatment is much easier to do since blood transfusions are super common and well es…

did they not have the same problem in doing the aids vaccine?

There isn't an HIV vaccine.

Re: Coronavirus Spike Protein Binder Design

#49

Earlier quoted context omitted.

I’m sorry to hear about your wife’s friend. But both examples you gave (people having to fight for further diagnoses of outside-case health problems) are really common with private healthcare in the United States too - we’ve just shifted the burden of cost of treatment/quality of life decisions to private entities who typically are only interested in furthering shareholder value. To give a personal anecdote as well:…

> I’m sorry to hear about your wife’s friend. But both examples you gave (people having to fight for further diagnoses of outside-case health problems) are really common with private healthcare in the United States too - we’ve just shifted the burden of cost of treatment/quality of life decisions to private entities who typically are only interested in furthering shareholder value. Having a profit motive is only a se…

> Having a profit motive is only a serious problem when there is insufficient competition. Otherwise companies that try to make outlandish profits would lose business to companies that offer better coverage for lower premiums by taking smaller profits.

This works in an idealized free market.

Health care is, for a variety of reasons, fundamentally incompatible with this, even if the powerful and wealthy interests within it are not actively working to destroy some of the basic premises of a free market (like equal information).

Re: Coronavirus Spike Protein Binder Design

#50
post #33
post #32

Earlier quoted context omitted.

The big cloud providers already donate a fair amount of compute (for example, some time ago I ran exacycle, which provided teams like FOlding@Home and Rosetta with extensive computing power. However, the economics of cloud are such that nearly all large-scale compute needs to provide revenue to the cloud provider for the provider to stay competitive. I've worked with the US gov't funding agencies in the past to make…

Governments have a staggering amount of computational power. Good will is nice and all, but are we putting our tax payer funds to an obvious public need?

Do they? I mean, technically the US gov't leases a ton of desktops (not great for scientific/technical computing), and they own a few supercomputers for specific needs (national defense, weather), but mostly they fund modest computational centers in academic environments. Before cloud, I worked in grid, and grids strapped together the many academic and government clusters, mainly for embarassingly parallel workloads.

I don't think the government has shown itself to be a particularly skilled operator of large computing environments compared to the large cloud providers.

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