Duda Jarek

Also China and probably others ... and minimizing e.g. expected number of casualties, this might be a reasonable behavior. Personally, if having opportunity to participate in such test, if only not having some nasty side effects, I don't think if I would have any doubts.

https://www.bbc.com/news/world-europe-53735718 Coronavirus: Putin says vaccine has been approved for use Two more Stage III (8, +1 "approved") in https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html

Over a million doses of Oxford/AstraZeneca coronavirus vaccine possible by September, says researcher https://www.reuters.com/article/us-health-coronavirus-oxford-vaccine-res/over-a-million-doses-of-oxford-astrazeneca-covid-19-vaccine-possible-by-september-researcher-idUSKCN24L1TW Also two more Phase III (to 6 + 1 approved) in https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html

https://www.nejm.org/doi/full/10.1056/NEJMoa2022483 General optimism and preparation for vaccine this December:

There was added "approved" on this vaccine tracker ... for military use, also in phase II:

From https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html , third vaccine has entered phase III:

https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html Phase III: 2 Phase II: 8 e.g. Moderna to start Phase III in July, Phase I: 10 Preclinical: 125+

Is there a problem with this https://en.wikipedia.org/wiki/Molecular_clamp - that proteins in virus have higher energy required for fusion? Just putting mRNA into a cell, shouldn't it produce the lowest energy protein? If so, are these two configurations essentially different from anti-body perspective? Would such immune system attack infected cells and/or virus itself?

https://news.sky.com/story/coronavirus-covid-19-vaccine-for-30-million-by-september-if-trial-succeeds-says-sharma-11990039

https://arstechnica.com/science/2020/05/the-ars-covid-19-vaccine-primer-100-plus-in-the-works-8-in-clinical-trials/

I see, there are many reasons China will probably be first - from 23th March: https://www.clinicaltrialsarena.com/news/china-covid-19-vaccine-trial-begins/ https://en.wikipedia.org/wiki/COVID-19_vaccine

Good discussion about covid19 vaccine development: https://www.ted.com/talks/seth_berkley_the_quest_for_the_coronavirus_vaccine A radical approach to speedup: "Should scientists infect healthy people with the coronavirus to test vaccines?": https://www.nature.com/articles/d41586-020-00927-3

It is hard to tell how to interpret it, but the life cost (also economical) is just too high to allow for 18 month trials to satisfy regulations - "casualties of waiting" should be included in calculations. If being at least a bit promising and excluding toxicity, I believe massive usage will start - to test it in the field in endangered regions.

https://www.jpost.com/HEALTH-SCIENCE/Israeli-scientists-In-three-weeks-we-will-have-coronavirus-vaccine-619101

Imperial Collage predictions for UK - to save lives with vaccine, it would be needed by November: https://www.imperial.ac.uk/news/196234/covid19-imperial-researchers-model-likely-impact/

Interesting, if I properly understand, there are two forms of the virus membrane proteins: the pre-fusion ones in virus have stored energy to enable fusion with cell membrane, the post-fusion in infected cell have lower energy ... and the problem is that they are a bit different from perspective of antibodies. While it is much easier to produce the lower energy form, vaccine based on it would not protect against free virus, only would allow to mark the infected cells - these molecular clamp polypeptides are claimed to allow to produce pre-fusion ones. It is aminoacid sequence self-assembling into double helix rod-like structure ... I don't understand how it can help forming meta-stable higher energy protein forms? I see that this higher energy meta-stable form is originally prepared in ER membrane, somehow encapsulated from inside - from https://en.wikipedia.org/wiki/Coronavirus : ps. It is usually assumed that there are nearly no ribosomes in cytosol (?) - that some viruses have these complex capsides e.g. using pH difference to get into the nucleus ... so is the above diagram correct, or does coronavirus RNA have to get to ER or nucleus first? Update: ok, it seems there are free ribosomes in cytosol: https://en.wikipedia.org/wiki/Ribosome#Free_ribosomes So the most questionable part in this Moderna vaccine - just mRNA if I properly understand (?), is getting it into a cell: So can free mRNA get into a cell? But generally it could only give this weaker (?) post-fusion protection (assuming they go also to external membrane - not only ER suggested by diagram above) ... and could be also made by just putting these proteins on a liposome - I have started this thread with. A related idea is just putting ACE2 on liposome - getting a trap for this virus, it couldn't resist with mutations ... ps2: Also, the diagram above suggests that fusion requires binding with multiple ACE2 receptors, hence their concentration is a critical parameter ... which is said to be modulated by some common medicines used e.g. by high blood pressure and diabetic patients - suggesting a hypothesis that this might be a reason for increased mortality for them. Good lecture with commentary:

Unfortunately we are no longer talking about a hypothetical situation from some utilitarianism economy textbook, but about a real one with daily deaths in thousands. Balancing medical trials, these deaths can be seen as casualties of waiting. mRNA is rather less toxic than the actual virus. If such vaccine would be e.g. toxic for elderly, applied to the young ones it could build a herd immunity (better than Johnson's way) - there are many ways to optimize the "economy of waiting" for the main priority here: minimization of the number of deaths. Anyway, there are probably ongoing dozens of trials to get a vaccine, in various regulatory environment (like China) - I believe that before November there will be widely used some vaccine, at least as phase III trial on millions in potentially endangered regions.

They skipped animal trials so maybe it could be quickened, especially that this is just injecting mRNA ... and that Trump wants vaccine before November elections. Personally I would gladly volunteer to such trials if having an opportunity - in current situation of likely soon being infected with the real virus.

From today: https://www.theguardian.com/world/2020/mar/16/first-participant-us-coronavirus-vaccine-trial-moderna-dose

"Researchers rush to test coronavirus vaccine in people without knowing how well it works in animals" https://www.statnews.com/2020/03/11/researchers-rush-to-start-moderna-coronavirus-vaccine-trial-without-usual-animal-testing/ Good video about mechanisms of COVID-19: https://www.youtube.com/watch?v=Eeh054-Hx1U

Sounds like you are writing about capsid (?), viral envelopes are rather not made of proteins: https://en.wikipedia.org/wiki/Viral_envelope They have some glycoproteins, which could be put on a liposome to get a fake virus ...

I am not saying about just releasing random proteins, but trying to recreate its viral envelope - doesn't it look like liposome? - part of the membrane of cell which produced it. Doesn't this viral envelope have something additional like proteins for targeting? If so, couldn't we just put these external proteins on a liposome to get a fake virus? Wanting to target enveloped virus in bloodstream, we need to target the envelope - or maybe it is just too difficult for immune system, so in practice it can only target infected cells? I thought ribosomes are mainly in nucleus and ER (...mitochondria, chloroplasts), that free ribosomes in cytosol are relatively rare in eucariote (?) and capsid's purpose is usually to get material to the nucleus(?) But still - how to get this mRNA into cells? If using other viruses, I believe it is extremely difficult/time consuming to make it work, and seems nearly impossible for mass production in millions (?) I have seen hypothesized that in November, being nearly identical suggests single point of origin - like jumping from an animal host (bat?). Fresh Science article: https://www.sciencemag.org/news/2020/01/mining-coronavirus-genomes-clues-outbreak-s-origins

Sounds interesting, but from one side delivering mRNA to cell's nucleus seems extremely difficult without viral envelope+capsid (?) Ok, they probably use envelope+capsid of other viruses, e.g. used in gene therapy (?) - but it's probably extremely difficult to take it scale required here (?) From the other side, this way immune system can only learn targeting infected cells (assuming they expose some material) - wouldn't it be better if it could directly target virus in bloodstream? Coronavirus is enveloped - where is the difficulty in just mounting its external proteins on a liposome to get a fake virus for immune system training?

Sounds interesting - some interfering RNA? The situation does not look optimistic here, exponential population growth continues ( https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 ) and standard vaccine development needs a year. In this moment the virus is still nearly identical: "The researchers also found that the eight complete 2019-nCoV genomes were more than 99.98 percent identical, " https://www.genomeweb.com/genetic-research/coronavirus-genome-sequencing-finds-distinct-genetic-differences-2003-sars-virus what is a big advantage for training immune response, but quickly mutations can start - especially with population growth. What other defense options are there? Wouldn't e.g. just putting its external proteins on a liposome work as provisional vaccine?

Developing a standard vaccine for coronavirus will take at least a few months - what might be too late. However, its sequence is already known, and is nearly identical - suggesting recent single point of origin for human host. So the question is if/how there could be quickly started production of some provisional vaccine - not perfect but fast to introduce? Also exploiting the fact that these viruses are now nearly identical. For example synthesizing its outside proteins and putting them on liposomes - would its introduction to blood have a chance to prepare immune system for the real virus?