The Coronavirus Replication Cycle

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КОМЕНТАРІ: 405

@doodoobearlove 3 роки тому

thanks for explaining so clearly n making sense for details as well. this is really helpful! thanks a million

@zuhairreza 3 роки тому

I am taking Virology, Bio 420, as a second-degree undergraduate at my college, the City College of New York, in New York, NY., and this was very, VERY helpful. Thank you SO much for this amazing video that explains the workings of the Coronavirus easily and in a simple way. Best wishes!

@affirmationsforsuccesstoda1831 3 роки тому

Love this! Thank you for sharing your knowledge

@moethekhine8482 9 місяців тому

Thanks a lot. I was struggling so hard to understand this mechanism as I didn't understand it at all during lecture at school. Your explanations are very clear and easy to understand. Sincerely thanks.

@drumerzubair4000 4 роки тому

Thank you to posting such a knowledge able video.

@jeffleuvenink4943 2 роки тому

So I was learning for my exam and I didn't quite get the discontinuous transcription part, but this video really helped so thanks!

@amadoukodioMD 2 роки тому

Thank you so much for this brillant and cleary explanation. Awesome 👌

@guinevierebeck683 4 роки тому

Thank you so much. Excellent explaination best video i've ever watched

@zainub1236 3 роки тому

This is the best explanation. Thank you!

@emmathomson3591 4 роки тому

Nice video - the receptor of the COVID-19 SARS-CoV-2 (which binds to the S1-CTD of spike) is ACE2. I think the video has likely been adapted from the replication of the related betacoronavirus MHV (mouse hepatitis coronavirus) which binds to CEACAM1 (via the S1-NTD of spike)

@deanmoncaster 4 роки тому

Thank you Emma I was sure the receptor was ace2 too. However I must compliment you on your movie work, I saw you in sense and sensibility this week and you were most agreeable.

@iamkeystroke 4 роки тому

@@deanmoncaster That's ace!

@alainpannetier2543 4 роки тому

Material taken from *"Coronavirus infection of the central nervous system: host-virus stand-off"* (mouse central nervous system), *Nature 2006* www.nature.com/articles/nrmicro1343 (this explains the mixup between CEACAM1 and ACE2)

@dwannthomas9543 4 роки тому

question: so does the virus binding to ACE 2 decrease the production of ACE 2? and what stimulates the production of the amount of ACE2

@bennymarshall1320 4 роки тому

Emma Thomson be smart

@gregmattson2238 4 роки тому

awesome video. was hoping you could follow it up with a video on how recombination of viral particles actually works - ie: how we actually got into this mess with COVID-19 in the first place. I'm also interested in the limits of recombination, whether or not recombination works only using RNA sequences whole hog, or if it is possible for recombination to mix and match sections of viral RNA at the nucleotide level.

@sepehrzadehmorshedbeik8779 3 роки тому

I am currently working on my final year pharmacy project. This video helped me a lot in understanding the concepts of viral replication!!

@hamzaali-ni8qg 2 роки тому

I m also working on ORF1AB

@sepehrzadehmorshedbeik8779 2 роки тому

@@hamzaali-ni8qg good luck akhi

@jycapuras 3 роки тому

Very clear explanation and illustration... Thank you very much!!!

@marcmatossian7453 3 роки тому

Binding to the ACE2 receptor has been linked to NRP1 and TMPRSS2 as possible cofactors and even independent of ACE2 viral binding. Although the ACE2 receptor is commonly seen as the necessary component for viral infection, research is being published to suggest NRP-1 as a possible binding site for the cleaved portion of the Spike protein.

@matsalme3133 4 роки тому

Lucid and easy to survey. Wonderful voice of the narrator.

@plasmafall2745 2 роки тому

thank you!this video used a really clear way to explain this.

@lazysloth888 Рік тому

Very clear explanation. Thank you so much 💓

@sariroth6038 3 роки тому

A very clear video, explaining simply and clearly the whole process. I was very wise from him

@jonicrow4929 4 роки тому

finally, some more in-depth explanation on the topic. Thank you. I thought the receptor was ACE2, though. I think CEACAM1 (also called CD66a) is an immunoglobulin which is also used for cell invasion by some coronal Hepatitis Viruses.

@inzepinz 4 роки тому

@@Thomaaasooo In what way?

@philosophicalinquirer312 4 роки тому

it is ACE2 - not sure what happened in this video

@abdeldayemmedani2153 4 роки тому

Thank you for this explanation thank you

@ayaafifi872 4 роки тому

Amazing technique ,impress me so much 🧐

@DoctorJammer 4 роки тому

Great video! Very informative

@puja8406 3 роки тому

Great video sir , very crystal clear explanation 👍

@naseemdilawar6507 4 роки тому

Excellent demonstration !!

@Jstar001 Рік тому

Great video! I was struggling to understand what on earth subgenomic mRNA was and how it was generated, this video has made it really clear.

@frediksterner599 4 роки тому

Excelent Describing, The best video that I watched

@norrahmed3381 4 роки тому

And me 💯

@michaelb1785 4 роки тому

Great video! Well explained. Thanks.

@blindcat35 2 роки тому

thanks - really helpul for me!

@praveenkant2825 4 роки тому

Thank You so much for this

@ThePutucri 4 роки тому

thanks for the clear explanation!!!!

@perparimbytyci6953 2 роки тому

Thank you do much, it helped me a lot

@MrNandanakumara 3 роки тому

Thank you! Finally understood sir!

@mekky1237 Рік тому

Thank you very informative.

@irwinlxrry 2 роки тому

Thank you! Very helpful!

@jimayla7446 Рік тому

I've found this video useful.... I have Virology exams to write next week. Thank you

@user-pc9si7wo7o 4 роки тому

Very useful video , thank u very much 🌹

@oibal60 3 роки тому

Thanks for this.

@timopihlajamaki7403 3 роки тому

A well made video, but it does have quite a few errors. First of all, as other people have noticed too, the receptor for SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2). There's also evidence that SARS-CoV-2 can use neuropilin-1 (NRP1) as an entry receptor too. The other error is in transcription of subgenomic RNA (sgRNA). In your illustration you state that -ssRNA is used as a template, and therefore transcription would happen in 5'-3' direction. Translation happes in 5'-3' direction, but transcription happens only in 3'-5' direction. This is why Nidovirales (including CoV) use +ssRNA as a template to produce -sgRNA which is then used as a template for +sgRNA, and that is used as mRNA for translation of structrural proteins and accessory proteins. You got the principle right, but I guess you mixed a few things on the way. :)

@user-ze6qx1py2l 2 роки тому

Clear, concise and educational video for a non biologist to understand the replications of the virus. Hope can watch more videos such as virus mutation (delta), vaccination working mechanisms.

@yuwan 2 роки тому

Wondering presentation, clear and catching points.

@LaughterChief 2 роки тому

this was amazing

@AK.ALMAHASNEH 4 роки тому

Thank you ... ✳️✳️❣️

@williamvilchezcruz 4 роки тому

Me encanto la explicacion :D , Thank YOU

@scottkolaya2110 2 роки тому

Great video, but do you know how long it takes in actual time between the receptor binding with the protein in the beginning to the end of the process there a new virus is released? And also how many copies get created from one virion? Thanks so much!

@themoroccangirls4933 2 роки тому

thank u but why we have a frame shift please🙏🙏🙏 can you reply because i have this part in my project

@martinfederico7269 3 роки тому

Very good video! but in regards to the discontinuous transcription, at 7:56 you say that the different length segments result from the polymerase initiating transcription at different sites, later you explain that it always starts at the end (3´ I assume) and then it ¨decouples¨ at different points (reattaching near the other end) thus giving the different length of each segment. I suppose this is the correct explanation, did I misunderstood what you meant at 7:56? Again, aside from that (unless I am mistaken) it is a really good video. thanks

@acluster3411 4 роки тому

Very clear explanation of the replication process in simple terms!

@williamjohn9622 4 роки тому

hi, very good video, thanks! could you provide a list of references to dive in, please?

@user-dj2ic2iz4i 2 роки тому

Awsome explanation

@salvadorhirth1641 3 роки тому

Very rich explanation. Subscribed.

@nebukenazar 4 роки тому

I want to ask about discotinious transcription at RNA (-) which create difirent Subgenomic mRNAs to translate viral structural proteins. How does transcription process regulate at difirent Body TRSs? Transscription ignores some parts (to create different mRNA+) of RNA(-) and pass to leader TRS. How? Thanks.

@jonathanmitchell8698 4 роки тому

Are the structural proteins translated directly into the Rough ER membrane? Do the viral envelopes form by a sort of reverse-budding into the ER lumen or are they created in some other way?

@nawaz600 4 роки тому

Very useful video 🙋‍♀️

@bok.1722 4 роки тому

Hello, what role does arginine have to do in the viral replication?

@ayamistarke2414 8 місяців тому

hello, this video was really helpful. could you provide some references in the future? :)

@aldrvxc1079 2 роки тому

*where did you get these **2:04** and **4:10** pictures? I checked the link on description but i didn't find it. Could you give me the articles link here? Thanks a loot btw 🙏✨*

@rokus100 4 роки тому

Thanks!

@korich7152 4 роки тому

Thank you for this excellent and detailed video. I wonder where the angiotensin converting enzyme 2 (ACE2) enter into the picture, as it looks to be involved in Covid-19 replication pathway somewhere.

@korich7152 4 роки тому

Thanks

@nebukenazar 4 роки тому

@@Thomaaasooo Video is not wrong - this paper explain mice infection / all of the mecanisms are some but ceacam is goning to be ACE2 at humans.

@xaviercompagnion5309 4 роки тому

i think the CEACAM-1 is the receptor for nervous cell and ACE2 for lung cell

@abc-fv6lq 4 роки тому

For entery spike protein attach ACE2 on type 2 pneumocyte and need cleavage proteas TMPRSS2. 😘

@deepneasy 2 роки тому

Thanks for the information. A question. How long does it take for this virus duplicate to complete?

@muntee33 4 роки тому

Question is, what hereditary (genome of mixed race/not ideally compatible blood types.) and external factors (environmental/electrical/RF.) can affect the preliminaries in how they operate? Should we absolutely avoid certain amino acids, proteins, blood ph?

@nacirnazeer2039 2 роки тому

mic drop explanation... good job

@gugulothsaikrishna1668 4 роки тому

can I get the reference notes or book from this video ??? pleasee

@fornello123 4 роки тому

How does the RNA ‘know’ which sub genomes to translate? How does it organize the proteins into a new virion?

@TheMagodana 4 роки тому

The RNA doesnt know, it's all driven by signals in proteins and RNA, through a series of RNA-protein, Protein-protein RNA-Rna interactions they assymble. This vedio is bit over simplified but the whole thing is much complex.

@philosophicalinquirer312 4 роки тому

The RNA has the equivalent of full stops and comma's. Thats like that leader TRS bit. Certain base pairs repeat or create "on/off" switches. The proteins are organized into new virons by eletrostatic and vaan der waals forces (weak force) interactions. In the case of Coronavirus - its actually quite weakly put together - hence huge sensitivity to detergents and 70% alcohol. (basically soap turns the virus into an emulsion completely destroying it) In contrast - something like spores of anthrax are actually tough as hell and last 40+ years in savage & harsh environments (strong covalent bonds make the structure and shell - not the case for such a virus as Coronavirus.)

@WadcaWymiaru 4 роки тому

There is only ONE answer: matter ability to self-assemble. Self-organization.

@jeanlatimer665 4 роки тому

good molecular detail

@aladinndrake110 4 роки тому

👍👍👍 fantastic. Thanks

@user-xi5qn8ev8l 3 роки тому

Various size of (-) subgenomic RNAs are generated first, and then they are used as templates for various sizes of (+) subgenomic RNAs. The fugure at 11:00 time point is confusing. However, Much thanks for this Video.

@japito0 3 роки тому

Right from infection or direct contact, how long does attachment and entry take? Days? Hours?

@link2012Philanthropist 4 роки тому

How can a frameshift to a different reading frame occur? Great video by the way! Very informative.

@TheMagodana 4 роки тому

Frame shift is usually a method in which most viruses including HIV make multiple proteins/ poly proteins from one transcript. There is a signal called the slippery sequence that slows down the ribosome during translation, followed by a pseudonot that pushes the Ribosome back one nucleotide, resulting in reading frame shift. Codons are read in 3s (bases) to give an amino acid, changing frame can result in different amino acid chain.

@r.guerreiro140 3 роки тому

@@TheMagodana So, this would be the basis for mutations?

@lucasqwert1 4 роки тому

Great Video! But how does the RNA dependent RNA Polymerase know if to stop on the different TRSs (TRS2; TRS7 etc.)? Is there a specific RNA dependent RNA Polymerase for every TRS?

@CatalystUniversity 4 роки тому

I'm note sure if it is known, but it is most likely a combination of secondary and tertiary structures that the RNA forms with associated proteins that facilitates the "jump".

@lucasqwert1 4 роки тому

@@CatalystUniversity thank you very much for your answer!

@robcordon97 4 роки тому

Catalyst University follow up question - what makes these structures functional sometimes but sometimes not? Where does the process become non-deterministic? Loved your video by the way, thanks for making it!!

@scottclark6674 4 роки тому

Ok I thought the SARS CoV 2 (COVID-19) initially binds to ACE2 receptors?

@davewilson13 4 роки тому

Scott Clark it does :(

@vasudeva9905 4 роки тому

Yes

@TheMagodana 4 роки тому

Yeah that's true

@cosmosradio 4 роки тому

How is this different than whats explained in this video? I'm being sincere and wish to learn. Rna is the Dna messenger, correct?

@samuel_prince 4 роки тому

Yeah! In human it's initially binds to ACE2 receptors and gains the entry but in mice it is by CEACAM1 according to me for experimental purpose they introduced this virus

@rafick8033 4 роки тому

Here in the pathogenesis discused about diffrent proteins that inhibiting normal inflamtory proteins lik IFN alpha n gamma which necessory to destroy virus....then what causes cytokine storm???? is there any specific viral proteins or lik bacterial superantigen that can bind with antigen-antibody complex in the T cell receptor site, cause excesive and non specific activation T cell and over production cytokine and lead to cytokine storm?

@cosmosradio 4 роки тому

My question then is there a way to alter what has been omitted so that the original rna messaging may continue? Even if the part thats omitted is forced to cycle back to attain rhe original memory? If possible would this not double the omitted forgotten strands.... or?

@vest7916 3 роки тому

I have a question about the translation of the RNA-string. Does the process end with both 1ab and 1a polyproteins? Or is it only if the frameshift occurs , that the polyprotein 1ab is made?

@leonardojoserichtzenhain5295 4 роки тому

Congratulations!

@shawnbalk7877 4 роки тому

I didn't find anything about SARS2 binding to CEACAM1. I thought that SARS-CoV, SARS-CoV2 (Covid-19), and HCoV-NL63 all bound to ACE2. BTW, I was reading about the angiotensin pathway and a little about coronavirus, and if you are taking high blood pressure meds, you might ask about aliskiren (which directly inhibits renin on its active site). ACE2, the cellular entry receptor for SARS2 (Covid) is downregulated from something I read in Nature (high impact journal). Angiotensin I and Angiotensin II are produced by and downstream of renin, respectively. While ACE coverts Agiotensin I to Angiotensin II, while ACE2, the target of Covid that gets internalized and degraded by cell entry of the virus, converts Angiotensin II to Ang1-7 (a vasodilator), owing to some of the pathophysiology of Covid (ACE and ACE2 have countering effects). However, since Aliskerin abrogates the synthesis of both Angiotensin I and Angiotensin II and downregulates ACE2 (presumably because of an otherwise positive feedback by the renin products), it may even have beneficial effects in slowing infection while still acting to lower blood pressure because there are fewer ACE2s on the cell membrane. Ask your doctor at least about your present BP medication at least. See: www.nature.com/articles/s41569-020-0368-x

@michael90754 4 роки тому

Hello, I am taking up microbio, just tackled virology recently (but got kinda canceled due to this pandemic) and I am kinda confused. Can the proteins be derived from the original genome? Accdg to the Baltimore system, I thought (+) ssRNA viruses can readily translate their original genetic material to derive proteins? Why is it here, the viral proteins were needed to be derived from the antisense RNA after going through the discontinuous transcription? Or can the proteins be derived both ways?

@mirigoldin5281 4 роки тому

Great explanation, does this mean that this viruse does not enter the host cell nucleus??? I mean all the replication process takes place in the cytoplasm?

@dccole9 2 роки тому

On the last slide you show, it looks as if the virion is taking part of the host ER with it as it exits the cell. Is this correct? I seem to remember reading about this when I was an undergrad.

@mooneymakes359 2 роки тому

Would it not be possible to treat the virus by having a protein that binds to a specific TRS at the very least would it not be able to weaken the virus as each protein would seemingly have a role to play?

@natesummer9575 4 роки тому

Would Interferon alpha 2B (recombinant) be useful ?

@diribataddeselegesse2717 4 роки тому

Great! difficulty is how to block only one step of the triplication

@philosophicalinquirer312 4 роки тому

very difficult - because virus uses our own cell machinery.

@elninonmg9397 3 роки тому

How does lysine effect viral replication?

@Perionian 3 роки тому

Hi, thanks for the video. In another video, it says that (-) strand subgenomic RNAs are transcribed from the (+) genomic RNA. These (-) strand subgenomic RNAs are then transcribed by RdRp into (+) strand subgenomic RNAs. Does this process happen as well? Also, can you please give more detail on how the no.6, no.5, etc subgenomic RNAs get created if the RdRp just skips to the leader TRS after reaching the no.7 TRS?

@Nile996 2 роки тому

I honestly think he made a mistake there as well. The subgenomic RNAs are (-), complementary to the original genomic strand. They then get capped and poly-A-tailed, therefore recognized as mRNA by the ribosomes.

@mimi-xw5se 4 роки тому

Amazing video thanks I love biology

@JohnDoe-vs7qf 4 роки тому

What's interesting is that the diagram you are using at 3:40 is showing that the sg mRNAs are coming directly from the full antisense (-) genomic RNA strand that is synthesized from the initial sense (+) genomic RNA, yet the diagram used at 8:48 was taken from Marle et al.'s 1999 paper, which contends a completely different mechanism for the sg mRNA synthesis. In their paper, they contend that the sequence goes as follows: sense (+) viral genomic RNA, to discontinuous antisense (-) sg RNA synthesis via RdRp 'jumping', to (+) sg mRNA synthesis finally. This was clearly outlined in Figure 5 of their paper. Therefore, it seems you are presenting two different mechanisms of sg mRNA synthesis. I have watched a lot of your videos and absolutely love them, so I am not trying to be difficult.

@MrAryanthaker 4 роки тому

Ya, he needed to finish the story by mentioning that the antisense discontinuous RNA are converted to sense before translation. Thanks for pointing out.

@tumeeambaga840 4 роки тому

Meaning there should be antisense to sense mRNA transcription?

@mrsvle 4 роки тому

You have it right. His description in the video was not correct.

@JohnDoe-vs7qf 4 роки тому

Tumee Ambaga Yeah, basically. After the discontinuous sg RNA strand is made (which is technically antisense), the RdRp protein initially made then helps make the complimentary strand of the antisense strand, therefore making the sense sg mRNA strand (5’ -> 3’ in its orientation), which can then be directly used in the translation of virus-related proteins. I’m almost 100% sure he read the paper and knew all of this, but simply needed to keep things simple & concise for the purposes of the video.

@juliablaszczyk8036 2 роки тому

In my opinion, first there is + ssRNA 5 '> 3', and then the sgRNA is formed, which is on the antisense strand. The antisense sgRNA is transcribed into the sense sgRNA. The sense sgRNA is translated. Let me know if I am incorrect. I will dive into that problem more deeply

@minimac721 4 роки тому

Excellent video, would know how long it might take from being exposed to being contagious. I work as a medic and if I was exposed at work how much time do I have before I am contagious and give it to my family???

@meslud 4 роки тому

probably 24-48 hours at least. err on the 24h side, if you're not sure. also, it could take a week or two until you feel symptoms.

@minimac721 4 роки тому

@@meslud awesome, thank you.

@mini17238 4 роки тому

Thank you

@ujlaminhas1 4 роки тому

what is the time duration of this replication cycle?

@westfield90 4 роки тому

Superb

@jongelb9603 4 роки тому

What controls Discontinuous Transcription from making ALL of the different types of proteins? There's got to be something that helps the transcription machinery decide which body TRS to stop at and which ones to run through. If i were a lazy viral RdRp, I would only make protein 7 and then forget about making any of the other ones.

@TheClaudiaHorizon 3 роки тому

What roles does adenosine triphosphate play in the replication of SARS-CoV-2?

@ThanhNguyen-kg9fp 3 роки тому

I was wondering how long process Replication Cycle will take???

@umakanni 3 роки тому

good information

@asinjitdas3113 3 роки тому

Is that pp1a, pp1b complex act as RdRp, as they both are engaged in replication @!!??

@vincenttelfer4206 3 роки тому

Excellent explanation, early understanding, can more than 1 cv19 virus infect 1 cell at the same time? And , can another cv19 virus infect a cell when another cv19 virus has already infected a cell?

@NewmiesDad 2 роки тому

6:28 - Definitely watch the whole video (multiple times if need be) but if there's one thing IMO that people should get out of this is the part about the viral RNA being transcribed into a multitude of subgenomic mRNAs. Then at 7:49 - it really makes the point of the production of DIFFERENT VIRAL PROTEINS. So when you hear NATURAL immunity is immunity to the MANY different viral proteins vs. the vaccine that makes one 'immune' to the spike protein ONLY - you understand the mechanism.

@price4freedom 4 роки тому

And is or does furan clipping different in other coronas?

@davidrefaat9467 4 роки тому

Does it attach only to this receptor(CEACAM-1) or other receptors?

@Zipilingui 4 роки тому

ACE-2.

@nullnull2945 4 роки тому

S2’ CD147 as well. Similar to malaria’s RBM

@kikuyekoyano923 4 роки тому

Great video, can you please post the references?

@YuehMusic 4 роки тому

I just can't figure out how a single mRNA produces multiple proteins? After the ribonsomal frameshifting (caused simply by the RNA's secondary structure ?) as you said, does it use proteases or some other substances, from the virus or from the host? Thanks for the video.

@royh7911 4 роки тому

Multiple proteins can come from a single mrna strand, it depends on how many base pairs are available on the mrna to be expressed. Usually the cell takes advantage of this by encoding multiple cofunctional proteins on one mrna strand

@blitz3dmusic 4 роки тому

Your question is really how a single mRNA can be replicated into multiple mRNAs each of different lengths encoding different proteins. It is the discontinuous transcription that does that. Notice that for each transcript the 3' end (- sense) now becomes the 5' end (+ sense). If I recall correctly ribosomes usually make one protein before falling off. Nevertheless this gets the virus a chance to express all the structural proteins. The non-structural proteins are encoded in ORF1a and b and if the ribosome happens to do frameshifting it does not fall off and causes ORF1b to be translated as well. The resulting polyprotein PP1ab is cleaved to form functional RdRp and other proteins. This happens first thing a cell gets infected btw before any of the discontinuous transcription stuff.

@pratuldesouza2244 4 роки тому

@@blitz3dmusic why are frameshifts occuring?

@blitz3dmusic 4 роки тому

@@pratuldesouza2244 There is a slippery sequence at the end of ORF1a just before b. Sometimes the ribosome gets caught on it and misses the stop codon.

@user-pc9si7wo7o 4 роки тому

@@blitz3dmusic thank u for explanation But i can't understand why +ssRNA converted into -ssRNA by RNA polymerase , while it readable by ribosomes and can directly translated to proteins