About the protein shape of Covid-19

[Ygggdrasil]

The journal Cell published online a report showing that SARS-CoV-2, the virus that causes the COVID-19 disease, requires a host cell enzyme for entry into cells and that clinically approved inhibitors of that enzyme can inhibit virus entry in experiments with cultured cells:

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically-Proven Protease Inhibitor
Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder, Nadine Krüger, Tanja Herrler,Sandra Erichsen, Tobias S. Schiergens, Georg Herrler, Nai-Huei Wu, Andreas Nitsche, Marcel A. Müller, Christian Drosten, Stefan Pöhlmann
Cell DOI: 10.1016/j.cell.2020.02.052
https://marlin-prod.literatumonline.../research/cell/CELL_S0092-8674(20)30229-4.pdf

Abstract:

The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor, ACE2, for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2and SARS-CoV infectionand identify a potential target for antiviral intervention.

The TMPRSS2 inhibitor they use in the paper is camostat mesylate. The drug is not FDA approved for any indications, but it is approved for clinical use in Japan. Efficacy in cell culture experiments does not guarantee that the drug will be safe or effective in humans, but at least it provides another lead to test in clinical trials.

 

[Paul C]

Italy is in the news, but the other European countries are affected, too. And they said it's now on all continents. (I guess they have forgotten to mention antarctica as exception, but who knows.) On Teneriffa is an entire hotel with 1,000 people under quarantine.

Noting there are many reports of Covid 19 disease occurrence, You may find this an interesting resource:Coronavirus COVID-19 Global Cases by Johns Hopkins CSSE

https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6

 

[pinball1970]

Italy is in the news, but the other European countries are affected, too. And they said it's now on all continents. (I guess they have forgotten to mention antarctica as exception, but who knows.) On Teneriffa is an entire hotel with 1,000 people under quarantine.

Hardly. Covid-19 basically behaves like influenza, and alcohol as well as smoking reduces body resilience.

The main mean factor is the long incubation period and the fact that people can carry and spread it without being sick themselves. And symptomatic ranges between nothing and severe. China soon officially will have the world's cleanest money!

I did not mean as part of a well rounded diet!

I meant as a prophylactic, there was an article that suggested alcohol inhibits respiratory infection in moderate use.

I will find it and see if it based on anything substantial in my view then throw it out to you guys.

 

[fresh_42]

I meant as a prophylactic, there was an article that suggested alcohol inhibits respiratory infection in moderate use.

I doubt this very much. SARS-Cor-2 resides on our oral mucosa where it replicates. So you would probably have to gargle with high percentage rum frequently. But I don't know whether alcohol kills it. It survives for days on surfaces, i.e. it is pretty strong.

 

[hagopbul]

lipid nanoparticle? Any one heard of it ?

 

[Paul C]

lipid nanoparticle? Any one heard of it ?

Yes. Actually, these are sought in bodily fluid samples in the course of performing a liquid biopsy. Also sought are extracellular DNA and stray parts of the chondriome. They suggest cellular destruction and may carry markers of disease such as infection or metastasis.

 

[Paul C]

I meant as a prophylactic, there was an article that suggested alcohol inhibits respiratory infection in moderate use.

I heard somewhere that gargling and spitting out an aspirin tablet daily inhibits respiratory infection. No proof of that, or studies I can find, but it's lore and generally as harmless as a daily dram.

 

[hagopbul]

Mrna-1273 what is this ?

 

[TeethWhitener]

Mrna-1273 what is this ?

mRNA-1273 is apparently the RNA vaccine that Moderna is working on for this strain of coronavirus. In this case, the RNA codes for the Coronavirus spike protein. When administered, the patient’s body uses the RNA to make the protein, which stimulates the immune response, preventing or mitigating infection.

On a somewhat unrelated note, this thread is all over the place. What exactly is the topic under discussion now?

 

[jim mcnamara]

@hagopbul started the thread and keeps asking add-on questions. Please create new threads on marginally related questions.

@TeethWhitener 's point is well taken.

The next digression will get the thread closed.

 

[hagopbul]

@hagopbul started the thread and keeps asking add-on questions. Please create new threads on marginally related questions.

@TeethWhitener 's point is well taken.

The next digression will get the thread closed.

My first goal of this thread is asking about synthetic methods to create antibodies

My second goal is to stimulate a talking between people and brainstorming

That why I am adding questions one after one in this thread

If it was too much I am sorry

 

[Ygggdrasil]

Two more structures published, including the structure of ACE2 in complex with the receptor binding domain of the viral spike protein:

Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2
Yan et al. Science 04 Mar 2020: eabb2762
https://science.sciencemag.org/content/early/2020/03/03/science.abb2762

Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein
Walls et al. Cell doi:10.1016/j.cell.2020.02.058
https://www.cell.com/pb-assets/journals/research/cell/Cell_S0092-8674(20)30262-2.pdf

 

[hagopbul]

I should make new thread for this but because I am not an expert in the field with little knowledge in it , I want to share this link with you guys asking about your opinion :

https://www.nih.gov/news-events/new...-project-defines-normal-bacterial-makeup-body

It is a link about human macrobiom project , could this help some how , the idea came to me while I am walking , could human macrobiom be related to Covid-19

Could help cure it ?

Best
Hagop

 

[fresh_42]

I should make new thread for this but because I am not an expert in the field with little knowledge in it , I want to share this link with you guys asking about your opinion :

https://www.nih.gov/news-events/new...-project-defines-normal-bacterial-makeup-body

It is a link about human macrobiom project , could this help some how , the idea came to me while I am walking , could human macrobiom be related to covid-19

Could help cure it ?

Best
Hagop

This is rather unlikely.

The best news is that China has the most data, excellent scientists, and low hurdles for tests. Together with the fact that many public and private institutions do research as well, and at least the public sector shares its results, we already have the best possible circumstances to find first a therapy, and second a vaccine. I'm sure there is nothing one of us can think of which hasn't already been thought by far more competent people.

 

[Ygggdrasil]

Here's a nice article from STAT news describing efforts to design protein-based nanoparticle vaccines (essentially constructing a protein scaffold to help display the spike antigen protein so that it can be better recognized by the immune system): https://www.statnews.com/2020/03/09...egos-with-proteins-to-build-next-gen-vaccine/

 

[Phil Core]

I am not a molecular genetists. However, via internet, have come across Chinese studies that indicate that the Coronvirus is different and more infectious because of a RNA nucleotide chain at the end - a marker. How hard is it to fashion a reverse RNA nucleotide that would match with the tail and neutralize it?

 

[Ygggdrasil]

I am not a molecular genetists. However, via internet, have come across Chinese studies that indicate that the Coronvirus is different and more infectious because of a RNA nucleotide chain at the end - a marker. How hard is it to fashion a reverse RNA nucleotide that would match with the tail and neutralize it?

It is possible to target specific RNA sequences using a technique called antisense therapy that is essentially what propose, an complementary RNA molecule that can bind to the RNA and interfere with its function.

However, I am not aware of any studies showing that a certain sequence near the end makes it more infectious. Do you have a link to the Chinese studies where you found this information?

 

[Phil Core]

Coronavirus Could Be a 'Chimera' of Two Different Viruses, Genome Analysis Suggests
https://www.sciencealert.com/genome...avirus-suggests-two-viruses-may-have-combined
ALEXANDRE HASSANIN, THE CONVERSATION
24 MARCH 2020

This does not mention that the changes are at the end of the RNA change. Do not remember where I picked that up.

I have read so much now that I am unsure where I read everything. There might have been more info some where else.

However, I believe it was some articles that you were mentioning that described the difference in the actual structure of the Coronvisus. These differences have to be RNA/protein relate.

RNA - protein - surface.

Tangential is https://www.foxnews.com/science/the-coronavirus-did-not-escape-from-a-lab-heres-how-we-know

I actually do not think that the "evidence" in the article supports the conclusion of the title. But regardless again there is a difference in the RNA structure of the current virus and others.

I know nothing about nucleotide analysis. How challenging is it to examine a 30,000 RNA chain?

All of the above is meant to direct some reflection as to whether a reverse trans DNA test it the way to go?

Within the week there has be mention of a blood antibody test - https://www.sciencemag.org/news/202...es-could-show-true-scale-coronavirus-pandemic

 

[Phil Core]

@hagopbul started the thread and keeps asking add-on questions. Please create new threads on marginally related questions.

@TeethWhitener 's point is well taken.

The next digression will get the thread closed.

Please let people say what they feel like they have to say. Others do not have to comment if they do not want to. If others do not comment then the tread is over - simple.

 

[TeethWhitener]

Please let people say what they feel like they have to say. Others do not have to comment if they do not want to. If others do not comment then the tread is over - simple.

From the terms of service for PF:
“Thread hijacks and off-topic posts:
Do not hijack an existing thread with off-topic comments or questions--start a new thread. Any off-topic posts will be deleted or moved to an appropriate forum per administrator or mentor discretion.”

 

[Paul C]

How challenging is it to examine a 30,000 RNA chain?

All of the above is meant to direct some reflection as to whether a reverse trans DNA test it the way to go?

A couple of thoughts.
A full and complete examination of the virus' RNA chain is exhaustive. A 30K base transcriptome offers a vast number of post-translation possibilities, in accord with host cell interactions. It's one thing to count bases or discover and illuminate the function of exon/intron regions, but once proteins are translated, hydrated, and start folding their angles are less straightforward. The nice thing about discoveries in molecular biology is that they come steadily and across disciplines, so an enzyme can be characterized in one species and a similar sequence can be found in an entirely dissimilar species. A chimeric RNA, suggests the article, implies more than one strain became simultaneously able to infect humans from reservoirs in different species. I think this view is overly complicated. Here's what I think happened: Through repeated and chronic exposure to animal virus reservoirs, our human responses to foreign matter withstand innumerable contacts with microorganisms. One occasion, though, a human host for whatever reason responds to viral RNA. Perhaps his cells' polymerase generates a few copies of the virus, a few enzymes, maybe makes it to a Golgi body where it is encapsulated and released. Henceforth, we've a virus that has characteristics amenable to re-enter healthy human cells and begin the cycle again.

On the subject of reverse trans DNA, I believe I heard yesterday this was one method under study, as an antisense marker of known SARS CoV2 sequences. The stereochemistry of such an approach is beyond me, but DNA is well characterized and quite stable as a reagent, so I gather that's a design that holds promise.

I'm wondering what proportion of seropositive Covid-19 patients are actually killed by influenza, and are patients routinely screened for the flu? Because, the threshold for concern with Covid-19 is so low!

Best wishes.