SARS-CoV-2 Structure (COVID-19 Coronavirus)
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- Опубликовано: 2 апр 2020
- A structural exploration of the proteins produced by SARS-CoV-2.
PDB FILES:
6VSB - Spike protein
6VW1 - RBD of the spike protein in complex with ACE2
6SGC - Rabbit ribosome stalled on a poly-A tail
6Y2E - SARS CoV-2 main protease
6Y2F - SARS CoV-2 main protease bound to an inhibitor
REFERENCES:
• Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C. L., Abiona, O., ... & McLellan, J. S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 367(6483), 1260-1263.
• White, J. M., Delos, S. E., Brecher, M., & Schornberg, K. (2008). Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. Critical reviews in biochemistry and molecular biology, 43(3), 189-219.
• Zhang, L., Lin, D., Sun, X., Curth, U., Drosten, C., Sauerhering, L., ... & Hilgenfeld, R. (2020). Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science.
• Fehr, A. R., & Perlman, S. (2015). Coronaviruses: an overview of their replication and pathogenesis. In Coronaviruses (pp. 1-23). Humana Press, New York, NY.
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Some of you asked how I modeled the RBD/ACE2 interface since there was no publication available at the time I made this video. Here's a follow up to show you how I did this in PyMOL: ruclips.net/video/hcnnKrlqa9M/видео.html
The paper is now published, so I show you a bonus interface interaction that involves one of the sugars near the end! It's SO neat!
For more PyMOL tutorials, check out this playlist: ruclips.net/p/PLUMhYZpMLtal_Z7to3by2ATHP-cI4ma5X
Thanks for your questions, comments, and the support!
Molecular Memory can u show us how u did it exactly in Pymol step by step and also can u show us how to make videos showing entery and replication process of the virus too .... i have been trying to make videos but keep getting confused in pymol chimera and all em softwares .... I wanna make animated videos for biochem best way to learn ... apparently .... I would love ur input if u can have a convo
You forgot to mentioned IT has full blown aids in IT 🤷🏾♂️
@@rogerwilco2 What an idiodic comment. From Wikipedia: "They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminiscent of the solar corona, from which their name derives." So the next time you have to take out your feelings of inferiority, don't criticize someone who is obviously light years ahead of you.
Molecular Memory buffone ti costa le buffonate
HI, I'm a journalist working on a multimedia package about the pandemic and how local researchers are involved in tackling different aspects. What I produce will be creative commons. Your videos look great and I'd love to use a few short clips. Am I able to do that? Thanks, Bruce, Otago Daily Times, New Zealand.
Just information, no bias, no political insight, pure knowledge. That's the kind of video and information i wish youtube and medias in general was made of. Thanks you for making this kind of video, we need a lot more of those.
You do know alphabet owns RUclips. You’ll never get what you’re asking in any consistent basis.
@@er5282 lol. .the video was good..fun to watch and informative.
But though I know next to nothing about these things I can see much of this is speculative. Results in this field are subject to large number repetitions of trial and error...and a lot less to theoretical formulation.
I think its going to be awhile before effective drugs are found.
There's a lot of uncertainty here
YES SCIENCE
@@bernardotellez3755 Like the honey badger, Virus dont care. Wonderful break from distracting spins. just shared facts.
Exactly my words
I'm an undergraduate student researcher. And, I have to say that this work is one of the very insightful videos I have ever watched. Thank you!
"Notice that it's heavily glycosylated..."
Yes. Of course. I know exactly what this means.
Not that hard to figure out
When I hear a term that I don't know, I start searching. But I presume that this is probably not what "normal" people do these days :q
Of course it was actually explained. It has suger coding 😂 try not to think sugar glazed donuts 😅
Just for precision sake here there is little more detailed description 😂en.m.wikipedia.org/wiki/Glycosylation?wprov=sfla1
your mom is heavily glycosylated
Very Professional - Short - clear and to the point. Short bite size lectures are usually more effective for learning than long lectures . Most folks are not able to focus on difficult material for longer periods when presented for the first time. Thank you.
I am a biotechnology student and would like to say that this video is what I was searching for! Thank you so much!
I'm just a layman, but that was really cool to watch. It's interesting to see how viruses work on the molecular level.
That was INCREDIBLE.
How do people get THIS good at presentation?
Excellent work.
I loved the extensive look into the bonding structure. I rarely see videos that show regions with full appreciation
I love your tutorials. I'm about to finish a PhD in molecular biology/biochemistry and started working for a gene therapy company. I've never been a strong structural guy, always found pymol slightly intimidating. With your videos I managed to locate and visualize the receptor binding domain of our therapy vector, adeno-associated virus. It's enormously helpful, I love it, gives so much information on what kind of mutagenesis approaches to choose and much more. Of course not to forget the fancy animations, which you truly master, that really add some wow to presentations! Thanks a lot for your effort in sharing your insights and helping scientists like me!
Ahh, this makes my day! So happy you found my tutorials helpful. Thank YOU for watching and taking the time to leave me such a nice comment.
@@MolecularMemory The time it takes writing a comment is absolutely insignificant compared to the time you spent making those clips. May I ask what you normally work on? Are you a full time structural biologist or is it more part of the bigger picture? Lastly, are you in academia or industry? Thanks a lot for your reply, I was also very happy that my comment didn't go unnoticed :) Cheers, Sebastian
Always amazed at you Pymol ability. I love this video. I've been reading all the journal articles.
Looking forward to see more videos like this explaining the enzymes how to work. Very good video~
The visualisations made it very easy to grasp. I have been looking for such detailed explanation.
Thank you for the extra extra detail! I loved this so much!
Fantastic and thorough video! Love the positive tone and messages :-). Thank you for your hard work. It clearly shows in the quality of the production.
This is the best video on SARS Cov-2 period.
I am a 11th-grade student and I love biology i could relate to sm part of the explanation, very n0ice and helpful!!
Rly Thx fr liking my comment, Are these the only the sources you have?? If any more are available pls just post it. Thx again, peace!
Computational biology, biophysics, and biochemistry. This video is an excellent educational resource for learning the immunological mechanism of SARS-CoV2 infection and replication. It also helps when you understand the terminology and the nomenclature used in the images within this video...which I do. Thank you whomever produced this video.
No wonder it takes high end video cards to model these interactions. This is really, really complicated 3d math being performed on large scale structures. Thank you!
Este vídeo es fantástico. Gracias por publicarlo en RUclips.
I'm an Engineer watching this video but all the chemistry made me open my high school chemistry books and recall all those concepts of biomolecular chemistry. I truly understood everything.....
Engineers always let people know they are engineers.
How can you tell if an Engineer is extroverted: when they talk to you they look at your shoes instead of their own...
@@hakureishrine as an engineer i can say it's totally wrong
Yeah i know your parents told u to become an engineer
@@tasis3835 Please explain how it's wrong?
Thank you Dr. Procko! This was amazing, super insightful and I learned a lot as always.
This was a truly marvelous video. Thank you so much! :) Stay safe!
This video is in great detail, appreciate it!.
Fantastic video ! It'd be really cool to show complenent C3b couple with antibody attacking the infected cell, and the MHC presenting the epitope for specific Ab receptors.
Finally made simple so that anyone can understand. Great video.
This is awsome, valuable information.
Thanks for providing the pdb ids. Thank you so much.
This is fantastic. Need more of this content!
MOST HUMBLY SPEAKING-I AM A GENIUS.
Helped so much to my Microbiology homework. Thanks for making that highly informative video!
Fantastic video. Awesome work. Keep up the good work.
I loved it. Beautifully explained. Its easy now to understand the virus-host interactions. Thank you !
Very goog explanation on understanding the molecular mechanism involved in a COVID-19 infection. I like the didactic way you explained the many interactions and hydrogen bonding in play during the infection as well as in the protease and its inhibitor
Amazing visualization. Looks complex.
an incredible video! thanks for the explanation
Excellent video, detailed and not 'dumbed down'.
Excellent presentation
Great job..most informative video 👌🏻
Geez that mechanism was beautifully done! 8:50
Simple yet interesting!! Helpful !! Thank you!
Excellent video
Fantastic job! Great explanation!
thank you for the interesting and informative video. May I know whether there is another area of the RBD that enhances viral endocytosis despite binding to the human ACE2 receptors??
My biochemistry class in college has finally come in handy to understand what she is talking about
First so detailed show up. Thank You
Amazing quality hands down, I’m a med student and this video was so enlightening. Thank you.
THX!
Can make some tutorial about protein dimer, trimer, tetramer process!
What will you suggest to me to read about it?
Super informative and very warm messages at the end. You just got me subscribed!
Another excellent and very informative video as usual.
Very good video! Informative and easy to follow
Excellent explanation.
This is a fantastic video, especially for someone trying to visualize it as accurately (given the ever-updating research) as possible. I'll have to watch your PyMOL tutorials -- I only have a working knowledge of chimera.
great work, congrates
Another excellent video. One conversation builder, however: I was under the impression that the ACE2 binding allowed for endocytosis, where the virulent RNA gets released after lysosomal breakdown of the shell. I know this doesn't impact the vaccine approach, but it does lend itself to several designer inhibitors instead for more broad spectrum virality reduction. Thanks again for the video, I'm working my way up to this level of Pymol utility.... Very slowly
Thank you for a great comment. Full disclosure-I purposefully omitted details of the fusion process as I didn't have the time to deeply research this aspect and feel fully comfortable presenting those details. The animations in this video were a heavy lift!
The animations you undertook were a awesomely heavy lift, and in such short order while juggling your other works. Sorry if I was nitpicking, I really enjoyed it and the depth was amazing.
No way! All of your comments are always welcome-I spent years nitpicking your work, it's time for you to share your knowledge with me!!
I found this very interesting. Animation, excellent. There won’t be a cure for a very long. This disease in my view will be seasonal. Just like the flu. Might as well get use to it.
No vacine.... must edited alll human .. legalize crispr for human use.. pacient zero is a 2 crispr edited child... most answer for human answer. . . Check geen...
#sarmBAN , covid make your tst to half, all must sarm buy ...
You are showing how ingenious the Lord designer is from atomic level. Thanks.
thank you for this amazing explanation
Nicely done and very informative. Some additional info re. description of the sugars. There are ~5-7X as many sugars on each side chain as depicted in the cryo-EM images. This technique only visualizes the innermost sugars. The primary function of the sugars is to interact with aqueous (water) phase and enable solubility and proper 3D structure of the glycoprotein.
Great video.
Just amazing .... awesome.
It seems like the first of the 3 RBD's is in a high energy state (flipped up) and wants to get to a low energy state through the first binding, i.e. an exothermic reaction. Then the remaining two RBD's are sent into a higher energy state. The endogenous proteolytic enzymes must sacrifice the higher energy state of one part of the peptide in order to create an upturned higher energy state at the other two RBD's. Then the other two upturned RBD's find a lower energy state by binding to the ACE receptor.
thanks for great informations
What is the overall charge or polarity of this spike protein ?
Great. Thank you
I second the nonpolitical praise commentary. This is what is needed, now. Also at 6:38, it is interesting how the virus essentially hacks and overclocks the replication process. Just my Information Technology perspective.
This is the best video by far thank you you genius
Great video, can I ask how to dock covlent ligand to a target? what software I should use?
Excellent video! Can you also talk about CD147 (Basingin) binding of SARS-CoV-2? Thanks in advance.
Great video, makes me want to start studying chemistry again
Is anyone else in love with the narrator's voice!? Her tone makes it way more interesting and engaging. Thank you so much for your great work 💜
Thanks for watching and for the kind words!
Remarkable! Thank you!
Nice content
Great piece of explanation. The idea of using a strong covalent bond to permanently deactivate the process of connection of the virus to the cell. Hope you progress quicly on it.
A question. I'm not a doctor/biologist, but an engineer which worked on the design of medical diagnostic/lab machines; what if you place a molecule at top of the domain, a molecule with a strong and multisided charge, inactive in itself, but able to skew all the hydrogen bonds in the area? They are so weak, I used to cell them "water bridges"...
Thanks for the excellent video.
You are very intelligent human being. I wish you are involved in the great feat of discovering the vaccine for Covid19 so that I can go out once more freely without fear. Your mind is so loveable!
loved it......☺☺☺☺
Thank you!
Loved it
Thanks!
Beautiful, absolutely satisfying. Let us pray that a vaccine can be made.
this explanation is the best ever..now I understand mechanism of this virus...thank you..
Nonsense - if you or anyone else really understood it we could
have cured the common cold by now.
100 years of research and we still can't cure the common cold of
which Coronavirus is just one example.
Nobody understands shit about this virus yet
Amazing
Thanks
What software did u use to this video?
Where does the "B-enzyme" 8:38 at come from?
This is incredible! Haven't felt so dumb in my life lol This was humbling
You can learn everything you need to know to understand this in about a month with the right book or with internet searches should you wish to do so.
How do they model proteins like that? How do they know how the ribbon tangles up in that particular way?
these are models. computer generated/assisted models. proteins do not actually look like that, they dont have nice distinguishable colors etc.. the alpha helices and b-sheets are representations to better make sense of the virus in a 3D-environment, otherwise the only other way to "see" them would be electron microscopy but that doesnt give such a nice image. So in reality, these models combine data from a lot of different methods to kind of grasp how the protein works and looks like. you have to maybe begin with easier structures and basic molecular biology like how aminoacids, fats and sugars look like, how they are build and then work your way up. this is a lot of chemistry and physics at this point basically and without a basic background all of this might be hard to grasp. things like covalent bonding, valence electrons forces like Van der Waals and hydrogen bridge bonding, to comprehend how and why proteins form the way they form.
Nice!!
I assume it’s chemical energy,,,what frequency do you think these RBDs are pulsating at? What’s the goal post that we bring our immunity down to,to meet the viruse
Great video in understanding something so complex. As a non biologist or medical background can the atoms of a virus be seen? Thumbs up already subscribe 👍
Can the virus be tricked into dumping its payload without docking? Does that S Protein resemble other Coronaviruses spikes, or other naturally occuring spikes?
The spike protein resembles SARS-1 2002/2003 coronavirus - although that has a weaker binding and although higher pathogenicity was less transmittable.
Short answer to the first question is no, there is no method to trigger virus to dump its payload and dont quite see how that would work (you would need to replicate a cell membrane with ACE-2 receptors, quite a task)
When the virus is isolated, the way to make it dump its payload is by destroying its surface membranes. Protease enzymes released and Lymphocytes would do this job ***IF*** they recognize the virus as a target.
Other that that - the virus is easily destroyed by disrupting its outer membranes in vitro outside the body easily using disinfectants. Of course, this doesn't work in vivo, within the body because those disinfectants destroy our own proteins and lipids (sorry Trump, but no, disinfectants dont work in vivo - or lets say they do, at our own demise)
@@philosophicalinquirer312 does the virus do most of its dirty work while on the surface of lung epithelial cells, and as such have no exposure to blood borne drugs? Once the virus is in blood, can we opsonize the viron, so wbc can kill it? Had followed Seattle genetics methods with interest.
Mind blowing i wanna work in progein designing field
Love it!!!
Very informative.... I have a question 🙋 can covid 19 has different s protein in different countries and how fast can a virus changes its genetic material.
Hello! Thanks for watching. How fast a virus can mutate depends on the virus. I'm not qualified to answer that one (I'm a structure gal myself) but there are researchers analyzing this, and you can view their findings here: nextstrain.org/narratives/ncov/sit-rep/2020-04-03 If the s protein gains mutations over time, it is possible for it to have some (usually small) structural changes over time.
I hope they find it fast with no red-tape.
Is it possible to use ACE inhibitors to stop ACE 2 fusion?
Por favor, podría ser en español?
What are the chemical reactions of covid 19 with human body and with hcl of stomach
I tried to follow but couldn’t understand beyond a certain point :(
Really a great job
Thank you for watching and leaving me a comment!
@@MolecularMemory You are welcome
Hi, noobie to structural biology. Can you explain what tools and how these ribbon diagrams and molecule structures are figured out? Where does one begin to come up with these diagrams if all you are presented with is a sample? Do we start with CryoEM? But how are the ribbon structures figured out, and how are the atoms/molecules discovered for that protein? If the software is coming up with the ribbon, then we have to know the atoms...is that NMR? Is there one tool that can do it all these days? Are you guys just protein folding based on sequence? Sorry, I know I'm asking for all knowledge on earth, but if you can just lay out the plan, and I will look up the details.Just don't know where to begin. Thanks. I have a BS in biology, but never learned all this cool stuff. Maybe a basics video laying out the steps to come up with these images and molecular overlay diagrams...it'll be popular.
Do you have any video to show how to identify binding pockets using Pymol? Thank you
Yep. Thanks for watching
ruclips.net/video/1vZDVbqRhyM/видео.html
@@MolecularMemory sorry, I don't understand. This video seems unrelated to my question. Am I wrong?