Abstract
The COVID-19 pandemic has demonstrated the need for exploring different diagnostic and therapeutic modalities to tackle future viral threats. In this vein, we propose the idea of sentinel cells, cellular biosensors capable of detecting viral antigens and responding to them with customizable responses. Using SARS-CoV-2 as a test case, we developed a live cell sensor (SARSNotch) using a de novo-designed protein binder against the SARS-CoV-2 Spike protein. SARSNotch is capable of driving custom genetically-encoded payloads in immortalized cell lines or in primary T lymphocytes in response to purified SARS-CoV-2 Spike or in the presence of Spike-expressing cells. Furthermore, SARSNotch is functional in a cellular system used in directed evolution platforms for development of better binders or therapeutics. In keeping with the rapid dissemination of scientific knowledge that has characterized the incredible scientific response to the ongoing pandemic, we extend an open invitation for others to make use of and improve SARSNotch sentinel cells in the hopes of unlocking the potential of the next generation of smart antiviral therapeutics

bioRxiv: Sentinel cells enable genetic detection of SARS-CoV-2 Spike protein

Related pdf

David Baker a co-author, so again likely to be SARS-CoV-2 related work still being done here even though task labels aren't explicit about it

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David Baker a co-author, so again likely to be SARS-CoV-2 related work still being done here even though task labels aren't explicit about it

That is really amazing stuff. It is like the dawn of the Age of Exploration, for our time.

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David Baker a co-author, so again likely to be SARS-CoV-2 related work still being done here even though task labels aren't explicit about it

That is really amazing stuff. It is like the dawn of the Age of Exploration, for our time.

It actually is. The Introduction is even more interesting than the Abstract. And then there's the Discussion section.
The in Silico part - that's us here

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I thought David Baker, as head of the IPD, was always on the paper authorship. At least I don't think I've seen a single paper from IPD labs/staff without Baker's name on it. Obviously I haven't seen them all. I'm probably wrong.
No mention of Rosetta or Rosetta@home on that print though.

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I thought David Baker, as head of the IPD, was always on the paper authorship. At least I don't think I've seen a single paper from IPD labs/staff without Baker's name on it. Obviously I haven't seen them all. I'm probably wrong.
No mention of Rosetta or Rosetta@home on that print though.

I've probably confused myself. Most of those named seem to operate out of SF, CA

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12 shocking images that show how bad the COVID-19 crisis is in India

https://www.usatoday.com/in-depth/news/world/2021/04/29/covid-19-crisis-india-display-these-shocking-photos/4886613001/

12 shocking images that show how bad the COVID-19 crisis is in India

https://www.usatoday.com/in-depth/news/world/2021/04/29/covid-19-crisis-india-display-these-shocking-photos/4886613001/

A friend of mine tells me in the place where he was born they had 476 cremations and 50 burials in one day. Official CV19 deaths that day: 3

The official figure is 3500 deaths/day. Across 36 states, that's 95 each, so 3 or 4 deaths per city/town, maybe 1 per crematorium.
Usual death rate is 27k/day.
If those numbers are true they wouldn't even notice.
NY Times suggested numbers are understated by 2-5.
Reality seems closer to being understated by 20-50x, not 2-5.
There's a national shortage of wood for crematoriums - they're applying for permission to cut down trees in parks to provide more.
Posting photos of crematoriums has been made a criminal offence - officially, there's no problem...

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A New Coronavirus May Be Jumping From Dogs to People, Scientists Report

https://gizmodo.com/a-new-coronavirus-may-be-jumping-from-dogs-to-people-s-1846935191

New Vaccine Blocks COVID-19 and Variants, Plus Other Coronaviruses

https://corporate.dukehealth.org/news/new-vaccine-blocks-covid-19-and-variants-plus-other-coronaviruses

Biden Administration Unveils $3.2 Billion Hunt For Pill To Treat COVID-19, Other Viruses

https://www.huffpost.com/entry/covid-19-antiviral-pill-biden_n_60cbf90de4b01af0c26e5662

A more readable piece at Scientific American on the KingLabs development of nasal/oral sprays we've seen before, utilising the research work we've done here at Rosetta

Artificial Proteins Never Seen in the Natural World Are Becoming New COVID Vaccines and Medicines

The way I'm understanding this - and please correct me if I'm wrong - is that vaccines don't prevent infection and replication and spread (reduce but not prevent), which means the virus is still circulating but causes much less serious illness and death. Continued circulation/prevalence, however, means the possibility of further variants and vaccine escape etc

But with this prophylactic spray, aimed at the Receptor Binding Domain (RBD) rather than the whole spike, it prevents infection because it out-competes the ACE2 receptor and neutralises the virus before infection.
No infection means no replication means no spread means no variants or vaccine escape and the virus dies out.

Is this right or have I taken it too far?
Because if it's right then it heralds the end of the virus rather than just protecting people while it continues on around the world

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Is this right or have I taken it too far?
Because if it's right then it heralds the end of the virus rather than just protecting people while it continues on around the world

It is almost a semantic difference. The vaccines could wipe out the disease if they were used. So could the nasal spray, just by a different mechanism.

The real question is will people use them?

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Is this right or have I taken it too far?
Because if it's right then it heralds the end of the virus rather than just protecting people while it continues on around the world

It is almost a semantic difference. The vaccines could wipe out the disease if they were used. So could the nasal spray, just by a different mechanism.

The real question is will people use them?

That's not what's being said about vaccines in the UK.
They're saying the vaccine can't prevent the original infection, but only begins to act after infection, during the incubation/replication stage.
So while it may partially act during that period, it acts most to reduce serious disease and onwards.
It doesn't completely reduce spread from the vaccinated person, because it can't begin to act early enough - reducing subsequent spread by two-thirds is one version I've heard.

What I'm understanding about this spray, if I'm right, is it goes into the throat/nasal passages and lasts several days so that if the virus is breathed in the spray out-competes the body's ACE2 receptors and combines with the RBD of the virus so that it doesn't infect the body in the very first place, meaning it can't incubate at all, nor spread or anything else afterwards.

I have to admit, I've had to read the original papers several times even to get close to understanding what they're saying.
They're incredibly dense with information that's been extremely hard for me to follow and take in, which is why I still have some doubt I've understood it properly.

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The way I'm understanding this - and please correct me if I'm wrong - is that vaccines don't prevent infection and replication and spread (reduce but not prevent), which means the virus is still circulating but causes much less serious illness and death. Continued circulation/prevalence, however, means the possibility of further variants and vaccine escape etc

Vaccines are basically training data for your immune system. The result is that your immune system will reduce the number of virus particles in your body more effectively, often down to 0. That's important because it reduces transmission of the virus, but also reduces the probability of successful mutation of the virus, so reduces the probability of more virulent or more transmissible strains being released. Every person that is infected is an incubator for potential new strains.

So vaccines do not necessarily stop the virus getting to you - that requries those you have contact with to be immune or not exposed - but a vaccine can stop the virus from causing you harm, and stop you incubating the virus and passing it on to others.

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That's not what's being said about vaccines in the UK.
They're saying the vaccine can't prevent the original infection, but only begins to act after infection, during the incubation/replication stage.
So while it may partially act during that period, it acts most to reduce serious disease and onwards.
It doesn't completely reduce spread from the vaccinated person, because it can't begin to act early enough - reducing subsequent spread by two-thirds is one version I've heard.

No vaccine is 100% effective. But they have wiped out several diseases, including smallpox. That is because if enough people take them, then the virus can't replicate enough and it dies out.
It will be the same thing with the nasal spray. It may be more effective per person, but only if it is used.
More likely, not all people will use it, and the virus will go on.

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The way I'm understanding this - and please correct me if I'm wrong - is that vaccines don't prevent infection and replication and spread (reduce but not prevent), which means the virus is still circulating but causes much less serious illness and death. Continued circulation/prevalence, however, means the possibility of further variants and vaccine escape etc

Vaccines are basically training data for your immune system. The result is that your immune system will reduce the number of virus particles in your body more effectively, often down to 0. That's important because it reduces transmission of the virus, but also reduces the probability of successful mutation of the virus, so reduces the probability of more virulent or more transmissible strains being released. Every person that is infected is an incubator for potential new strains.

So vaccines do not necessarily stop the virus getting to you - that requires those you have contact with to be immune or not exposed - but a vaccine can stop the virus from causing you harm, and stop you incubating the virus and passing it on to others.

Thanks. I'm getting that part.
It's as you say, though - it requires infection first before the immune system detects it, then acts against it. And until it fully does its job some reducing amount of replication and spread can still happen, though the most important part of vaccines being that it stops serious disease and more affecting the host. But some reduced amount of replication and spread still happens - said to be about 1/3rd of the amount an unvaccinated person would spread.

What I'm understanding about the spray is that it covers the nasal and throat passages and has a high-affinity to combining with the RBD of the virus, locks onto it, thereby neutralising it and preventing infection of the ACE2 receptors in the first place, so no infection. And no infection means no replication or onward spread at all as well as no entry to the body for the immune system to fight.

So it's not an alternative to vaccines but another weapon in the armoury, useful for example to teachers in a classroom or for going to a mass-attendance event like a concert or sporting event

I'm not sure if I'm explaining myself well enough here.

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That's not what's being said about vaccines in the UK.
They're saying the vaccine can't prevent the original infection, but only begins to act after infection, during the incubation/replication stage.
So while it may partially act during that period, it acts most to reduce serious disease and onwards.
It doesn't completely reduce spread from the vaccinated person, because it can't begin to act early enough - reducing subsequent spread by two-thirds is one version I've heard.

No vaccine is 100% effective. But they have wiped out several diseases, including smallpox. That is because if enough people take them, then the virus can't replicate enough and it dies out.
It will be the same thing with the nasal spray. It may be more effective per person, but only if it is used.
More likely, not all people will use it, and the virus will go on.

I'm not talking about vaccine effectiveness at all, but you've made me think that, for those who aren't able to take the vaccine for various medical reasons, the spray can be an alternative.
And it's just struck me that, for those whose immune-system is suppressed or doesn't work so well, it'll do its job irrespective of the individual.

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That's not what's being said about vaccines in the UK.
They're saying the vaccine can't prevent the original infection, but only begins to act after infection, during the incubation/replication stage.
So while it may partially act during that period, it acts most to reduce serious disease and onwards.
It doesn't completely reduce spread from the vaccinated person, because it can't begin to act early eno
ugh - reducing subsequent spread by two-thirds is one version I've heard.

No vaccine is 100% effective. But they have wiped out several diseases, including smallpox. That is because if enough people take them, then the virus can't replicate enough and it dies out.
It will be the same thing with the nasal spray. It may be more effective per person, but only if it is used.
More likely, not all people will use it, and the virus will go on.

I'm not talking about vaccine effectiveness at all, but you've made me think that, for those who aren't able to take the vaccine for various medical reasons, the spray can be an alternative.
And it's just struck me that, for those whose immune-system is suppressed or doesn't work so well, it'll do its job irrespective of the individual.

The pill form is designed to do the same thing except make it available more wisely, ie Dr's offices, pharmacies even School Nurses and in Churches on a pre-approved walk-in basis. It would also go the 'last mile' for places like Indian Reservations and people only seeing Dr's once every few years. Both the spray and pills could also be adjusted on a yearly basis, much like the flu virus is, to account for any new variants that pop up as needed.

That's not what's being said about vaccines in the UK.
They're saying the vaccine can't prevent the original infection, but only begins to act after infection, during the incubation/replication stage.
So while it may partially act during that period, it acts most to reduce serious disease and onwards.
It doesn't completely reduce spread from the vaccinated person, because it can't begin to act early eno
ugh - reducing subsequent spread by two-thirds is one version I've heard.

No vaccine is 100% effective. But they have wiped out several diseases, including smallpox. That is because if enough people take them, then the virus can't replicate enough and it dies out.
It will be the same thing with the nasal spray. It may be more effective per person, but only if it is used.
More likely, not all people will use it, and the virus will go on.

I'm not talking about vaccine effectiveness at all, but you've made me think that, for those who aren't able to take the vaccine for various medical reasons, the spray can be an alternative.
And it's just struck me that, for those whose immune-system is suppressed or doesn't work so well, it'll do its job irrespective of the individual.

The pill form is designed to do the same thing except make it available more wisely, ie Dr's offices, pharmacies even School Nurses and in Churches on a pre-approved walk-in basis. It would also go the 'last mile' for places like Indian Reservations and people only seeing Dr's once every few years. Both the spray and pills could also be adjusted on a yearly basis, much like the flu virus is, to account for any new variants that pop up as needed.

Not sure if it was clear in the article or not, but by targeting only the RBD rather than the whole spike, it covers both past and future variants. Very low likelihood of a variant escaping it.
And it's not just the RBD of SARS-CoV2 it targets, but it also addresses the original SARS and MERS and, so I read elsewhere, 4 entire strains of flu, not just variants.

This section of the article talked about it a bit, but it's more explicit in the full papers that led to it

Yet even as those trials were progressing, the virus was spawning a new wave of variants with the ability to evade some of the antibodies triggered by the first generation of vaccines. So Walls went back to work, designing a new and improved nanoparticle. Instead of copies of just the SARS-CoV-2 RBD, this version had a mosaic of four different RBDs: some from SARS-CoV-2, some from the original SARS virus from the early 2000s and some from two other coronaviruses. This broad spectrum of RBDs elicited a robust antibody response against all coronaviruses tested, including the most elusive of the variants.

The vaccine from this same platform, that's recently confirmed funding for Phase 3 trials, is looking to replace the annual flu jab based on 2 initial doses and 1 booster jab 2 years later.
It's quite some advance on the mRNA vaccines that are currently out there, while dealing with flu at the same time

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The vaccine from this same platform, that's recently confirmed funding for Phase 3 trials, is looking to replace the annual flu jab based on 2 initial doses and 1 booster jab 2 years later. It's quite some advance on the mRNA vaccines that are currently out there, while dealing with flu at the same time

Now THAT might be really close to encouraging alot more people to get the shot!!