Coronaviruses 101: Focus on Molecular Virology

[@jonassekamane]

INTRO 0:19 - Human CoVs; CoV spillover to humans 5:13 - SARS vs. COVID19 8:45 - Talk overview 1. ENTRY 10:10 - CoV structure; spike conservation 14:41 - Spike and ACE2 interaction; protease cleavage 18:30 - CoV-2 spike residues 2. REPLICATION & GENE EXPRESSION 20:08 - 2019-nCOV annotation; 14 ORFs and 27 proteins 24:05 - Ribosomal frameshifting 26:38 - Sub-genomic mRNAs with shared 5' and 3' 29:06 - Shared transcription regulatory sequences 32:13 - CoV replicase; polymerase, capping and proofreading 34:08 - Exonuclease; viruses with >20kb genome 36:14 - Loss of Exonuclease; lethal mutagenesis 38:58 - Exonuclease and methyltransferase 3. Replication-transcription complexes (RTCs) 40:54 - Interconnected double membrane vesicles 43:32 - Vesicle formation 44:32 - Proximity labelling; Characterizing RTC proximal proteome 50:20 - Accessory genes 52:01 - Assembly of nucleocapsids into virions 4. Immune interactions 53:31 - Little or no interferon in cells; delayed interferon singling 57:39 - Short lived antibody and memory B cell response OUTRO 59:38 - Key open basic science questions

[@Luemm3l]

thanks for the timecodes, much appreciated!

[@sudharsana2874]

Its great to have time codes for a lecture.

[@MrsEwalani]

Q: Is sunlight able to kill viruses and bacteria? Does humidity affect the transmission? I've seen published medical documents that dispute what msm is issuing by script.

[@priyankasrinivas463]

Thank you

[@Stefan-gh7xr]

Virusses do not exist, they are exosomes. Dr Stefan Lanka, Dr Andrew Kaufman, Dr Thomas Cowan. Many many others

[@douglasstemke2444]

I took a virology course in graduate school almost a decade ago, what an incredible distance we have come. As a microbiologist myself I really appreciate putting your lecture up.

[@nbox9570]

Sir.i dont know about virology.But i hav a doubt can the caspid remove from RNA of virus without any damage?

[@nbox9570]

Sir, i dont know about this subject.but a doubt can capsid remove seprately from RNA without any damage in capsid?

[@douglasstemke2444]

@@nbox9570 I think this capsid literally assembles on the RNA itself, so I would think it unlikely.

[@gazmasonik2411]

How do we know the genome of the virus?As someone on the west isolated or finally done the 4 gold standard tests? We were just told the Chinese mixed RNA from the liquid in 7 of the lungs of 200 infected with whatever. But had a test before they had anything tangible. Can't believe anything they say. So who an when was wuhan a factor. There's possible cases from September! ? Só why bat nonsense is being talked about its not real science face it.

[@gazmasonik2411]

No pangolins? What was the intermediary? Not straight from bats no matter how good the novel.

[@kotsaris87]

Despite having no background in medicine or biology etc, I found this lecture really informative and easily understandable

[@Lrover16]

Thank you for this. I am a Candian biochemist stuck in Brazil. I decided to help the local authorities out. This brings me up to speed. I shared it among the English-speaking doctors as well.

[@SuperArkleo]

The manner in which material is presented is exceptional. To pack such amount of information in just one lecture is evidence of years of teaching the best students.This is an excellent example of excellent teaching for all teachers in academia

[@sailingchloe2330]

What a beautiful, clear minded, articulate, logical, level, educated, balanced, reasoned and highly intelligent voice. Very many thanks!! A perfect lecture.

[@jlcooper841]

Amen!

[@disturbingdevelopment4308]

Prof. Glaunsinger is a brilliant teacher. This presentation was extremely coherent and well put together. Thank you.

[@tomk6090]

@Fat Albert How many Chinese students would be lost at Berkley if she did?

[@TopGunMan]

@Fat Albert Perhaps because circumstantial evidence is for conspiracy theorists, not scientists.

[@James-fe7wd]

@@TopGunMan "Circumstantial evidence is used in civil courts to establish or refute liability. It is usually the most common form of evidence, for example in product liability cases and road traffic accidents. Forensic analysis of skid marks can frequently allow a reconstruction of the accident. " Guess investigators and lawyers are just a bunch of 'conspiracy theorists' too.

[@Stefan-gh7xr]

Virusses do not exist, they are exosomes. Dr Stefan Lanka, Dr Andrew Kaufman, Dr Thomas Cowan. Many many others

[@johnmulhern2833]

@@Stefan-gh7xr all quacks

[@juancarlosllaurado4514]

Even not being among the intended audience, i´ve been able to follow most of the lecture and have learnt quite a lot from it, and it´s really interesting, many thanks

[@fhhfhdfdhhdhhdfhdf138]

should be on primetime tv

[@juancarlosllaurado4514]

@ferzy09 if anything, this proves you didnt´t understand it

[@juancarlosllaurado4514]

@ferzy09 actually not

[@garyraab9132]

A deeper look into any form of nature is fascinating, and we all would benefit from a better understanding in many ways. Better appreciation for our place in the biosphere, more insights into maintaining health, and maybe, just maybe, some insights into the human brain which could lead to improved social behavior.

[@joanblond8527]

@ferzy09 Nothing is going to prove intelligent design. The only thing that might cast a measure of doubt on evolution by natural selection is a bio-mathematical approach which shows that 3 billion years just isn't enough time to generate the observed (and growing) level of complexity in organisms. Unquestionably, evolution is a real and powerful mechanism. There may, however, be some surprises that lie ahead. (There always are!). All theories (including Darwin's) have a range of convenience.

[@rcsz229]

Many thanks for this. As a clinician, this sort of exposition is incredibly helpful in gaining a better understanding of what we are trying to manage (treat?). The link between basic science and clinical medicine is always a challenge and this sort of background knowledge is invaluable when thinking about what we are seeing in patients.

[@yeny7194]

This explanation was amazing! I'm an undergraduate student, only in my 2nd semester of biochem and was able to keep with a lot of it because it was very well explained. I loved it, thank you, and also thank you to all the scientists working tirelessly to fight this.

[@shanemoe9098]

Trust me. This whole hour of the video is worth watching. The professor details every key note about coronavirus. (I am not a virologist).

[@baladevisetty1011]

An Outstanding Lecturer. Thank You Professor Britt Glaunsinger.

[@mayuri2365]

It took me complete 4 hours 45 min to understand this 1 hour lecture

[@cruze7778]

Likewise!!

[@anthonyroberson5199]

LOL don't feel bad it takes me about 5 hours to understand a one-hour lecture also LMAO

[@LambsyLamb]

Really? Took me an hour mostly because I'm a freak for zoonotic viruses! 😂

[@ranisharoni75]

Isn't this the deepest KZbin video ever? Britt is the Goddess of viruses

[@selfcensorship1]

Was boring in the beginning, and then it turned insightful, educational (not only regarding Coronaviruses), interesting and some other adjectives too. Glad I found such a high level source on KZbin.

[@humanearthling4661]

@ Self Censorship....Please keep looking.....

[@ruairidhmcmillan2484]

Studying viral biology at UG level. This is a really straight and detailed presentation. Thank you.

[@docimjad]

This is one of the most amazing talk i could ever come across about the structural details of Corona virus in context of mutational potential and probable targets for drug development. I might borrow some knowledge for my own understanding and spreading of awareness in here countries bereft of educational and research facilities and governmental intent for it. Thank you for this Leviathan of a task.

[@MichaelAlexander1967]

This is an incredibly fascinating presentation. I am so grateful for your commitment to the in depth understanding & logical explaination of this data to both the scientific & lay community. Phenomenal work!

[@MR1977.]

Can anyone share the time stamp for when she addresses how a respiratory virus penetrates the hosts brain cells causing them to run out and buy all the toilet paper? Or is that a different lecture?

[@davidbee7060]

Lmao

[@James-fe7wd]

It infects spinal cells and moves to the brain through them.

[@zubairkhalid685]

I was looking for something like this from some time ... Thank you for providing the authentic scientific information amid this info-demic where research data is hard to find on these media platforms 👏👏👏

[@asap2334]

Thank you very much Dr. Glaunsinger for such a great lecture

[@jayt6857]

Prof. G. Thank you for the wonderful, insightful presentation. I have to point out one thing. ACE 2 is an enzyme and has substrates (angiotensin 1 and 2). There is no ACE 2 receptor. SARS Covid 2 uses ACE 2 as a "receptor" to enter the cell. So ACE2 is a "receptor" for SARS Covid 2 and one may call ACE2 an SARS Covid 2 receptor. It actually functions as an acceptor. Pharmacologically, a receptor, upon being bound by a ligand, should trigger a cascade of biochemical/physiological reactions. Virologists use the term receptor differently.

[@mypajourney2878]

As an undergrad biology major, I really enjoyed this in depth and straight forward overview. Thank you for making and uploading this and allowing me to apply and enhance my knowledge!

[@PowlinManuel]

Great discussion, I am an Immunologist. I learned a lot from listening. Thank you.

[@francinebaker737]

Great lecture. Very informative. I would love for Dr. Glaunsinger to give a follow-up lecture. Now that it has been almost two months with 10x more cases and more information I would love to hear her take on what's happening now.

[@user-pt-au-hg]

lecture seems very well put together, but it's really over my head without some background information, but I can see the work involved with putting together such an informative lecture, which is appreciated. :)

[@jakemccluremd]

Well done. Refreshing to see some virology 101 long-form presentations to counter a lot of the misinformation out there.

[@AutumnBreeze115]

Thank you Dr. Glaunsinger.

[@RamismTamoid]

You are a Heroine! You deserve recognition a Medal of Honor!

[@marioamendola1796]

best video seen so far on SARS-CoV-19!

[@eastwestcoastkid]

mario amendola Check This week in Virology-also excellent

[@infinitysalinity7981]

It's called SARS-CoV-2. The disease is COVID-19.

[@eastwestcoastkid]

Infinity Salinity correct 30 kB in size RNA single strand positive..

[@BreakyTime]

this is fascinating. I think virology is my new free time obsession lol

[@uzairelalumiere]

@51:25 Please elaborate more on the association of INF and role of IFN inhibitors on viral accessory proteins.

[@conradhalling3984]

Thank you, Dr. Glaunsinger, for that excellent introduction.

[@milespasta1100]

Absolutely fabulous you presented the science extremely well, until we understand fully the biochemistry we cannot create a cure. As a former biochemist and now a doctor. I applaud you on a fabulous presentation.

[@adhirajghosh364]

Brilliant video maam!!!

[@robinorhysrhys1562]

This is too complicated for me and there are so many parameters to look at. The key takeaway from this lecture is: - the delayed immune response which I imagine is associated to the fact they give a range between 2-14 days for symptoms to appear. Is it fair to say for those who get infected taking longer incubation, would end up getting severe/critical symptoms and disease than for those showing up symptoms earlier? How can this be mitigated? The solution seems to be within the body itself, just that it is not 'ticking' the right way.

[@groove9tube]

Very nice compilation of current knowledge of SARS-COV-2 molecular virology. As a retired biomedical scientist, makes me want to put on a white coat and get back at the bench.

[@kasiviswanathanvenkatraman8268]

Nice lecture. Steady flow of information. Well organized. Thanks.

[@charlieevergreen3514]

As a layman, I want to thank you for a very interesting talk on the virus' mechanisms. I have probably 20% or less of the prerequisite knowledge to fully understand the contents, so, though I undoubtedly missed a number of nuances, I feel I could explain the top tier of info you provided. Thank you for making an accessible talk without paring it back too far. I'm stunned at the tactics of the virus at each stage of it's cycle, and,frankly, equally stunned that we can collectively discover and understand them. Good job to all involved. Thank you, and keep up the good work!

[@Exnay777]

Excellent...I would suggest that a pointer of some type be used to highlight the specific areas as you present each slide/page. Allows the viewer to more readily 'see' the area being discussed and therefore absorb more...lol

[@BrawnyBuddha]

My bored-ass took full-fledged Cornell notes on this whole lecture.

[@MoveInSilence2444]

Lol I was bored and just listened. You are preparing for a blue book test lmao!

[@HenryMcGuinnessGuitar]

I'll be watching this a few times. Learning so much in a day or 2. I'm trying to get my head around the different classification systems...

[@hawk16-85]

Would you be able to send me your notes?

[@wichetleelamanit6195]

For an hour of lecture, I have learnt a lot of coronaviruses and it is very useful. Thank you so much, Professor.

[@robertschlesinger1342]

Absolutely superb lecture by an expert with encyclopedic knowledge of molecular virology. A very interesting and informative video.

[@miJ007]

Another theory of mine that I’ve been contemplating for many of years. I try to modify it little by little. Deals with cell regeneration and the destruction of harmful bacteria, viruses and cancer. As humans we can be severely impacted by sound, particular frequencies can alter our perception, destabilize out mood for the better or worse. An example on how our perception and mood cause specific cells to aid us or harm us just by hearing sounds or specific frequencies .here are minor examples, if a person hears a particular crying of a baby one can either be concern with mixtures of depression, horror which then triggers certain synapses within our receptors to alter out mood. The sound of our lover can trigger a sexually aroused feeling. That certain specific frequency of a loved one in pain can cause a whole array of chemical imbalances, from nausea, depression, anger, confusion. If I go as far to say that if animate frequencies can cause anything from extreme joy which cause certain molecules to be released within us then inanimate sounds as well can cause, frightening , joy, confusion, anger… etc. an example if a person is all of sudden is caught of guard by the massive sound of an explosion it will cause an elevation of symptoms, which can cause a lot of people to become sick for a short or for a prolonged time. So, if humans can be affected by frequencies so imagine a particular recording of subatomic harmonic frequency of a specific terrifying sound or the specific frequencies that human bones generate when they are repairing it self or the specific time when bones are being produced at birth. That specific frequency could in theory awaken dormant cells to fully start regrowing a lost limb. All cells create their own distinctive sounds in how they travel throughout our body. cells know how to communicate which each other and other cells and when a foreign molecule enters our body the specific molecule or molecules generate their own frequencies, whether those molecules be animate or inanimate. Every cell has its own unique frequency. This just a minor theory for which I have more to explain. So by now it is safe to say that if frequencies can cause us to be heal or harm us. Let say that a person has a virus in a body or some cancer or a foreign molecule which is harmful and can cause death. If one were to isolate for example , specific types of cancers or Ebola or corona19… etc in a controlled laboratory to find out at what specific frequency a certain type of cancer dies at for example just letting it die all on its with out a host just letting it plainly die. Recording the frequencies from the initial beginning of the experiment all the way until it starts to die to its last moment. The whole point is to purposely let it die an animate molecule. To capture the frequency when it’s all healthy an wandering around inside host an extracting a sample out of a host until it dies. So now that the frequency is now recorded, what might you think could happen if one plays that specific moment in time when the virus is dying. Being able to narrow and calibrate the minutes that can cause the virus or viruses to molecularly become sick all due to hearing it self, one cannot dismiss the notion that a virus doesn’t have emotions or is somewhat pragmatic because it does if it wasn’t true then it wouldn’t multiply it self to further its existence. A virus is either an incompetent or highly intelligent molecule one or the other, but one can’t deny that it’s alive. I have more on theory on constructing the recording devices and where one might be able to hold such experiments. Keep in mind bacteria, viruses are alive until they aren’t.

[@tahirbashir5535]

What a lecture?? Not only in context of Covid19 but also in understanding to pathophysiology of virus infections challenge in the future ahead after current drastic challenge. I recommend for incorporation of it in the pathology Curriculum word wide. NEW Normal scenario paradigm 🤗

[@npmwislab]

unnerving to hear such a knowledgeable calming voice describe this horrific time. our current global sadness, pain, and death deserves all the transparency labs and specialists can honestly pour out of their brain.

[@craigshelton5903]

Outstanding lecture, Dr. Glaunsinger!

[@davidsoldier1182]

Thank you, Britt, for producing this outstanding review. I'm sending the link out to our colleagues. (Dave Sulzer, Columbia Medical School)

[@bobf5360]

25% recombination rate for a +sense RNA virus is...terrifying.

[@TKO67]

makes one wonder if this was not manipulated a bit by humans

[@disclafs]

Thank you very much Dr. Glaunsinger for sharing your outstanding presentation! It is very detailed and understandable!

[@RandomNooby]

very easy to understand and lots covered

[@jessiedoggie1]

This wonderful lecture is well above my level of comprehension. It would be great if Dr. Glaunsinger could present a youtube lecture addressed to the lay person showing how SARS CoV-2 could be defeated.

[@reneirzz49]

Thank you so much! This is very informative yet easy to understand! Nice presentation!

[@Hammadgigr224]

Excellent lecture having deep understanding of molecular virology

[@bryanceballos1296]

Thank you, Dr. Glaunsinger, for this lecture

[@jeffinalaksa1]

Thank you for posting this Dr. Glaunsinger. It was just what I was looking for to understand the mechanisms of the virus, and how Remdesivir might work.

[@joeswan]

Great session

[@jayagopalkrishna8790]

Thank you . Was looking for this information for all long time.

[@nahirsoto1949]

I wish this could qualify for CE credits

[@katyhamlyn3983]

this helped so much with my virology case study! thank you so much

[@bayuk82]

Cool.. Free Lecture. High Quality. God Bless You

[@juanreza4500]

At around minute 33, the RNA replication process should state clearly the two steps: synthesize negative strand from the original positive strand, then synthesize a new positive strand from the negative strand.

[@ableone7855]

Excellent presentation. Very clear and precise speaking style. Good job!

[@jathish]

I'm dentist and not a virologist, most of the talk was understandable. as a layman my query is how significant is ACE2 receptor in the pathogenesis.my second query is how different is the pathogenesis of the virus in young healthy individuals who are silent carriers.

[@tnoulm]

ACE2 receptor role is very well established. It serves as a docking station for viral particle and mediates the fusion of its envelope with the cell membrane allowing viral RNA enter the cell. The role of ACE inhibitors or other drugs and conditions that result in more (or less) of ACE2 protein present is controversial. While it's an attractive hypothesis that standard ACE inhibitors known to cause increased accumilation of ACE2 on cell surface can be increasing one's chances of getting infected (or worsening the prognosis for infected individuals), there are results both supporting this hypothesis and rejecting it. For more of excellent medical science on COVID-19 - watch this webinar: kzbin.info/www/bejne/gJXFZ2qbedCer8U (start at 14:30)

[@jathish]

Thank you.... I was wondering if breathing exercise has any affect in improving the lung health and thereby delyaying or even preventing the viral pathogenesis.

[@Luemm3l]

the mechanisms by which virus genomes rely on their host and how the transcription machinery is modified is really fascinating.. especially the discontinuous transcription and the Exon protein... . I enjoyed this very much, thank you.

[@databang]

Thank you professor. The more I think about viruses I’m fascinated by their evolutionary phenomenon, and difficult to un-imagine as an organism with a nefarious plan.

[@humanearthling4661]

@ databang -- "They" are not organisms per se. They are exogenous particles that result from the REACTION of the body to ANY bacterium that excites the Human Immune system and they signal that the immune system is DOING ITS JOB of protecting the organism. I cannot imagine WHY , when the Public is seeking answers they can understand about this alleged Corona virus Pandemic , this lecturer, like someone being asked what time it is, delivers a lecture on how to build a watch. .. The public well KNOWS, that those who have college graduate degrees are Educated, but come on.....

[@Luemm3l]

@@humanearthling4661 can you stop spewing nonsense while adults have fruitful discussions under this fascinating lecture? Thank you.

[@humanearthling4661]

@ @@Luemm3l -- And you BELIEVE you're doing the public a favor, is that it? Why don't you let the public decide for themselves which one of us is telling the truth?

[@fengli2066]

Very informative lecture! Thank you, Dr. Glaunsinger

[@luismatheu4226]

great Presentation is there a lis of cited literature beside the slide?

[@aliislam5105]

Very Brilliant of your Discussion Professor. I would be interested to know, what are the underlying aspects of such tremendous diversity in viral strains.? can we attribute the phenomenons of Epitope transformation and genetic variability due to absence of proof reading mechanism.? or some species mediated interactions in response to which viral pathogenesis has become stronger.? and do we have some counter act approaches to fight these virruses.? I would like to have your expertise in this regard. Thank you.

[@lingen2193]

Thank you very much for this awesome lecture! Thought I know a thing or two about gene expression, but I stand corrected. This stuff is just mind blowing.

[@junviatorlifeingermany1836]

Awesome lecture! Could you please upload more about Coronavirus? I would love to learn more about it in a molecular level. Thank you so much!

[@defaultname992]

Thanks for doing this. Watched full video.

[@BushCampingTools]

Excellent presentation, thanks for posting.

[@GrowBagUK]

What would be your reply to scientists and doctors who are suggesting that CV-19 is an exosome?

[@a2e5]

Exosomes are only similar to viruses in that they both carry something wrapped in some membrane and that both get sent out by exocytosis. Saying exosomes make people sick just don’t make sense because… well we all make them with what’s written in our genomes. And CoVs obviously have a different genome.

[@canarylogicstudios7567]

The 'doctors' stating this is a psychatrist. Not a medical doctor. Do not fall for Russian Troll propoganda. 1. Exosomes don't have foreign DNA. 2. You don't build up antibodies against exosomes as they are not foreign to the body. In a German town 15% of people had antibodies against SARS-Cov-2. 3. If you actually looked on Wikipedia and other sites about exosomes, you'd know they disintegrate as soon as they leave the cell membrane, but here we can see the viruses are external to the cell.

[@PraveenKumar-co2vl]

Excellent...quick updates. thank you

[@BushCampingTools]

Who could give this a dislike??? It was great. I'm not a virologist although did spend a lot of time at uni purifying viruses and making antibodies LOL but later became a neuroscientist LOL, it's a great lecture for all scientist or not.

[@findout7505]

A great lecture!! Quiet complicated!!

[@IvayloGogov]

Hello I would like to understand several important topics, and I'm not able to find suitable information about it. Could you try to help: Where I can see, or understand the construction of Covid-19 - as vertical structure analyze from the Spike to the center of the virus. I would like to understand how the protein types and components are compiled and contained in the relation from center to outside the virus and opposite. Most of the places I see - top is spike protein, then we have envelope proteins, then what is bellow that in direction to the core of the protein, how relations are formed-combined. Is there any functional relation to that vertical organization? What about the rest of the proteins, where I can see them compiled and organized in a structure. I'm trying to make a 3D model, but some of the proteins, I cannot find information how to organize them properly. I would appreciate any suggestion or help. Thank you!

[@salvadorhirth1641]

Bacteria defend themselves from bacteriophages by producing restriction enzymes that recognize a palindromic segment in the viral genome, often no longer than six pairs of nitrogenous bases. Perhaps specific restriction enzymes capable of recognizing and cleaving one palindromic segment in the +mRNA from viruses could be isolated and delivered to cells via liposomes and fusion peptides, to hopefully cleave viruses in the cytoplasm of cells.

[@RUNDMC-555]

is there any special reason why CV did not effect humans up to very recently in our evolutionary development ? are they common in many animal species and id there anything interesting about the species they evolved to infect ? is there any reason to believe CV would have special characteristics that may lend its use to biological weapons use ? in particular with regard to its huge information load with a view to say genetic warfare ? there has yet to be a CV vaccine for sars or any CV is there a specific resaon for this ? why would immune memory not give immunity or protection for this specific virus even if anti bodies decress over time? what determines immunity post immune response

[@felipedigregorio3948]

Thank you so much for this presentation. Im very far away from being the intended audience but it has been very informative in a time where we hardly get detailed information on what we are facing

[@evelyne7071]

Great presentation

[@sm0000]

Great explanation....stay safe everybody 💫🙂

[@nilanabijan9705]

Hi I wanted to ask about a proper enzymatic assay for RNA Dependent RNA polymerase activity that we can use in the lab for testing antiviral activity and it has no radioactive thing in it

[@Thomaaasooo]

at the moment i am on kind of a crusade pointing out mistakes in youtube videos which try to explain molecular biology of coronaviruses. most of them contain multiple errors which realy bothers me. this was the first talk i really enjoyed and was backed up by actual research from start to finish. really interesting, detailed, easy to follow talk with acurate information. you did a great job! thank you

[@innovativegenomicsinstitute]

Thanks!

[@davidschmidt6013]

Think a lot of yourself, don't you.

[@infinitysalinity7981]

You can spend your whole life on that crusade and the endless stream of internet bullshit will never end.

[@thedoomlord5853]

hey, im a student that makes a project for school about the recent coronavirus epidemic. your video is a huge help for me. but i have one question, i did not understand what is helical nucleocapsid, can you explain it for me agen?

[@haiqinyan5953]

RNA genome + nucleocapsid protein = nucleocapsid

[@rajeshchheda456]

Dear Britt, what is exact role of Furin in the process of Covid19's lifecycle/entry into human cells? Please shed some light on this aspect.

[@joetapia4315]

This was beyond my Biotech Cert 1 knowledge but this was extremely insightful. As a RN this still interests me a bunch.

[@jayt6857]

Prof G, you stated there is a delayed interferon response in coronavirus infection. Can it explain the "reactivation" observed clinically? We have seen some patients were getting better then suddenly got worse, even died.

[@scholar2310]

Thank you for this very useful resource and information. Bullet points I wrote (please refer to the original video and articles for accuracy): In viral entry, spike protein binds angiotensin converting enzyme 2 receptor and transmembrane serine protease correceptor in SARS/CoV-1 and possibly in COVID-19/CoV-2. Promotes fusion of viral lipid envelope with lipid cell membrane. 30 kb (huge) single strand RNA (+) genome encoding for 27 proteins with structural and non-structural functions. Continuous transcription of non-structural protein genes into polyproteins that are later cleavaged. Discontinuous transcription of genes encoding structural proteins accounts for high mutation rates (up to 25%), both unique features of SARS-CoV2 within RNA (+) viruses. Viral RNA-dependent RNA polymerase is required for transcription (CoV replicase). Host eukaryotic factors are used for translation. (?) CoV replicase requires exonuclease activity for proofreading. Loss of exonuclease promotes genomic viral instability. SARS-Cov1 forms interconected intracellular vesicles "Replication and transcription complexes, RTCs" that protect from host exonucleases and eukaryotic viral sensors. RTCs are enriched for example in Nsp1 protein, a key coronavirus pathogenic factor that binds 40S ribosome subunit and blocks translation of host RNAs, favoring translation of viral RNAs and delaying interferon response in cells. Nsp1 KO coronavirus is a hypothetical vaccine strategy. SARS/CoV and MERS induce very few interferon response in most cells compared to other viruses. Multiple coronavirus proteins might delay type-I interferon signaling. Coronavirus requires accessory proteins for replication in vivo but not in vitro. Those accessory proteins include many interferon response factors (important consideration for research experimental design). Viral exoribonuclease can excise nucleoside analogs making virus resistant to certain drugs that target the viral genome. Therefore, an exoribonuclease inhibitor combined with nucleoside analog might synergize against CoV-2. COVID19/CoV-2 was transmitted from bats into a yet unknown animal vector that then infected humans. Estimates of many (5000) coronaviruses in bats highlight importance of understanding their basic biology in preparation for future transmissions to humans (not all bat coronaviruses can reach humans as they require the right mutations and an adequate intermediate vector). Neutralizing antibodies against coronavirus seem to be short lived. What type of immunity can we get from vaccines??

[@ambikamandal9229]

Very informative lecture. Thankyou.

[@abdulrhmanhGndy]

great lecture, but where is the link that the prof. mentioned?

[@nilanabijan2281]

Can you please tell me the RdRp gene of the SARS-COV-2

[@thegreentimesartstudios3327]

hi. there is s slide @ 40:20 :00 showing that detail.

[@lildon112]

This was a really informative and well-presented lecture, thanks for sharing! All of our accumulated knowledge on coronavirus biology really stresses the importance of funding basic research on infectious diseases even when they're not yet an immediate threat.

[@gamefuler]

32:08 I have questions about the TRS sequences; 1. Since the ribosome needs to reach the TRS of a sequential gene first, wouldn't the highest product transcript always be at the front? (I.e gene 2's product would be in higher concentration than gene 5?) 1.Another question is that if you had an exact copy of this TRS sequence with its own gene sequence of a random protein that is completely detached from the viral +mRNA strand and floating around in the cytoplasm, would it still be used and copied randomly? -My idea being that we can use a similar process to make viral workhorses and bypassing the need to electroporate E. coli/ use competent bacteria to introduce non-host oriented gene products via vectors. Still would need a way to stop the host cell from lysing open though... Maybe some form of latent bacteria and somehow manage to mass-produce non-virulent strands of viruses to infect vats of cells...

[@MichaelEatonAMDG]

I watched this over a year ago. I am still left wondering if and how origin in bats is determined, as opposed to just the bats being a particularly good place to find viruses that exist elsewhere in the virosphere.

[@rickeastburn9037]

TRUTH IS.....THEY DON'T KNOW WHERE VIRUSES ORIGINATE OR IF THEY EVEN EXISTS. ALSO, MUTATION NEVER LEADS TO DARWINIAN EVOLUTION WITH GAIN IN FUNCTION AND "JUMPS SPECIES" WHICH DEFIES ENTROPY!!! THERE ARE NO LAB TESTS THAT CAN IRREFUTABLY DEMONSTRATE A VIRUS!!! THIS IS ALL SPECULATION AND HYPOTHETICAL!!!!

[@shawncaskey9186]

Thank you for being a teacher.

[@constancetse2275]

really thank you for sharing all this knowledge!!!

[@YonathanEmmanuel]

Thanks for this lecture. Very thorough! Wondering if the more conserved fusion domain of the S-gp, or the polybasic linker would make a good target for mAb therapeutics?

[@jimball816]

fantastic video. great visual aids. also link to more lay info. superb