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Studying Coronaviruses: Vectors to Vaccines

00:00:02;29 My name is Tracey Goldstein,
00:00:04;17 and I work at UC Davis School of Veterinary Medicine.
00:00:07;03 I'm a Professor in the Department of Pathology,
00:00:09;09 Microbiology, and Immunology,
00:00:11;04 and Associate Director of the One Health Institute.
00:00:14;28 And what I do is really studying diseases in animals
00:00:19;08 and trying to understand how they may spill over from animals into people.
00:00:23;23 A good example is this coronavirus outbreak right now,
00:00:25;21 where it's affecting people,
00:00:27;13 but we understand that the virus likely came from animals.
00:00:30;17 My name is Koen Van Rompay.
00:00:32;28 I work at the California National Primate Research Center
00:00:35;15 at UC Davis.
00:00:37;23 What we're trying to do is create
00:00:39;16 the most effective vaccines.
00:00:41;06 We are also trying to develop antiviral drugs
00:00:43;03 to treat people who are already infected.
00:00:47;16 When there is a new viral disease,
00:00:49;13 the first thing is you have to know
00:00:51;16 what virus it is.
00:00:52;23 You want to know who your real enemy is.
00:00:56;11 In the old days, the methods were very slow --
00:00:59;15 techniques like electron microscopy.
00:01:03;21 These days, with sequencing the viral genome,
00:01:05;20 within a few days you can usually find out
00:01:07;19 what kind of virus is causing a new epidemic.
00:01:11;23 So, when you sequence the genome,
00:01:13;15 you can start to look at
00:01:15;28 where there might have been a mutation,
00:01:17;11 and that will tell you what parts of the viral genome
00:01:19;15 are important, for example,
00:01:21;10 to enter human cells.
00:01:23;18 In many of these animal viruses,
00:01:25;20 they're able to infect animal cells,
00:01:27;19 but they don't have the same machinery
00:01:29;09 to infect a human cell.
00:01:31;12 But RNA viruses, like ebolaviruses or coronaviruses,
00:01:34;23 they... you know, their genomes
00:01:36;28 are a little bit more unstable.
00:01:38;11 They're sort of always changing.
00:01:40;12 These big changes in the genome,
00:01:42;12 you know, they probably are happening all the time,
00:01:45;00 and sometimes they're random,
00:01:46;08 but every once in a while,
00:01:47;26 a change might occur in a part of that genome
00:01:50;16 that allows it to suddenly become,
00:01:53;07 you know, infectious in a human.
00:01:58;16 To develop a vaccine against some new infectious agent,
00:02:00;20 we can really learn a lot from the natural biology
00:02:03;07 of the virus.
00:02:05;02 In order for a virus to infect a human cell,
00:02:07;07 it needs to be able to bind to what we call
00:02:09;23 the receptor.
00:02:11;06 So, it's sort of like a lock and key.
00:02:13;10 When you think about coronaviruses,
00:02:14;29 you know, the spike protein,
00:02:16;14 which is the proteins on the outside of the virus...
00:02:18;19 we know that that's important for the virus
00:02:20;25 to be able to enter the human cell.
00:02:23;28 Once you know that,
00:02:25;13 you want to see,
00:02:26;24 which part of the virus should I use
00:02:28;27 in the vaccine construct?
00:02:31;25 What we try to do with the vaccine
00:02:33;26 is to come up with a strategy
00:02:36;12 that mimics a natural immune response
00:02:38;15 to infection.
00:02:40;26 It can either be by using
00:02:42;25 a live attenuated version of the virus
00:02:44;29 or taking some part of one of the proteins.
00:02:48;07 We really want to have something
00:02:49;27 that's specific against the virus,
00:02:52;11 but then has minimal cross-reactivity
00:02:54;19 to normal host proteins,
00:02:57;15 to minimize the chance for any side effects.
00:03:03;16 In 2016, when Zika virus broke out,
00:03:06;24 different primate centers...
00:03:08;28 we started working groups.
00:03:10;12 Something similar is now also starting
00:03:12;13 for the new coronavirus.
00:03:14;17 People have been really, really forthcoming
00:03:16;12 with new information
00:03:17;27 as it's becoming available,
00:03:19;19 sharing it even before it's been published.
00:03:22;14 We are going to have meetings
00:03:24;22 to really share our progress
00:03:26;29 and brainstorm experimental designs.
00:03:29;06 Soon, one of the first centers is actually going
00:03:31;17 to infect some monkeys with coronavirus.
00:03:35;22 We want to study diseases in animal models
00:03:37;28 that mimic the human disease.
00:03:40;23 We move this up from mice and rats
00:03:42;26 to higher species.
00:03:44;12 The species that's most...
00:03:47;12 closest to humans are actually non-human primates
00:03:49;08 such as rhesus macaques.
00:03:52;08 And they are usually the final step
00:03:54;20 for moving something into human clinical trials.
00:03:59;21 Human trials are done in different stages.
00:04:02;11 Phase 1 trial is to see, is it safe?
00:04:05;04 If that looks promising, then you go to a Phase 2,
00:04:07;22 where you test it in more people.
00:04:11;10 And the Phase 3 trial is kind of the first one
00:04:13;12 where you really want to look at,
00:04:15;12 does the vaccine work?
00:04:17;15 Does it protect against infection?
00:04:21;07 If we can all communicate
00:04:22;27 and we can collaborate very rapidly
00:04:24;19 -- we can share protocols --
00:04:26;14 that's kind of how we can make progress a lot faster.
00:04:31;29 I think during an outbreak,
00:04:33;16 it's very much a day-to-day response,
00:04:35;21 trying to understand how to get ahead of the curve
00:04:37;23 and control the problem.
00:04:39;16 But after that is when, really,
00:04:41;24 the big work begins.
00:04:43;18 Many of these diseases that cause pandemics
00:04:45;29 come from wildlife.
00:04:47;21 And our world is changing
00:04:49;18 really, really quickly.
00:04:51;14 We're moving into places where we didn't used to go
00:04:54;09 with our animals:
00:04:55;19 cutting down forests to make space for farms
00:04:57;09 or going into caves for mining.
00:05:00;11 Our behavior is what's facilitating, likely,
00:05:02;11 the spillover.
00:05:04;00 What we've been doing is sampling in all these places
00:05:06;12 around the world.
00:05:08;04 We focus on bats, rodents, and primates.
00:05:10;16 So, what we wanted to do was
00:05:12;21 specifically look and see
00:05:14;11 how many different coronaviruses
00:05:16;00 we could find in the different species.
00:05:17;21 And what was really interesting is,
00:05:19;11 despite us sampling all of these different taxa,
00:05:21;24 about 98% of the coronaviruses that we found
00:05:25;05 were in bats.
00:05:28;17 And then we mapped the diversity of the bat species
00:05:31;16 that we found those coronaviruses in.
00:05:34;02 So, sort of a hotspot map.
00:05:35;25 It's got the dots of where the viruses are,
00:05:37;21 and then colors of where we found
00:05:39;28 high diversity of the different bat species.
00:05:42;15 And that is useful because it can help us to
00:05:45;05 project where we might find other coronaviruses,
00:05:47;08 if we know where those bat species are.
00:05:50;21 The investment that we put in infectious disease research
00:05:54;05 pays off --
00:05:55;22 more than just that one particular disease
00:05:57;14 that you study,
00:05:58;27 but really by improving the overall knowledge
00:06:00;23 of infectious diseases of the immune system.
00:06:03;17 What there needs to be is
00:06:05;19 sustained research support
00:06:07;19 for these things before, during,
00:06:09;27 and after outbreaks.
00:06:11;09 The outbreak's over, and then,
00:06:12;28 you know, that funding goes away,
00:06:14;12 and then vaccines sit in labs
00:06:16;11 not being completed and not being trialed.
00:06:19;06 I think we need to figure out a way to not do that,
00:06:22;14 not have this boom and bust,
00:06:24;16 but be always supporting that type of work.
00:06:27;22 If you could sequence the genomes
00:06:30;19 of, say, a bunch of different coronaviruses,
00:06:32;29 how many different cell types can they infect?
00:06:35;26 And then, you know,
00:06:37;08 what would you have to do to change them?
00:06:38;24 You could potentially, over time,
00:06:40;11 generate data that would start
00:06:43;12 to maybe show you some things
00:06:45;27 that you could predict.
00:06:47;10 We can use that existing knowledge, that database,
00:06:49;09 to really come up with interventions
00:06:51;12 a lot faster to attack that new disease.
00:06:54;04 If we can understand more about the viruses
00:06:56;21 that are out there,
00:06:58;10 and have therapeutics and vaccines
00:07:00;07 and other things in place,
00:07:02;07 we can be better prepared to respond
00:07:04;05 to the next thing
00:07:07;03 versus scrambling every time
00:07:09;03 that something new pops up.

This Talk
Speakers: Tracey Goldstein, Koen Van Rompay
Audience:
  • General Public
  • Educators of H. School / Intro Undergrad
  • Student
  • Educators of Adv. Undergrad / Grad
  • Researcher
  • Educators
Recorded: February 2020
More Talks in Viruses
All Talks in Viruses

Talk Overview

When an infectious disease outbreak happens, medical workers and public health officials mobilize, but there are also teams of researchers that snap into action. Dr. Tracey Goldstein and Dr. Koen Van Rompay are both actively involved in different initiatives to find answers surrounding the COVID-19 epidemic. They talk about the process of studying coronaviruses and other infectious diseases, the steps taken once an outbreak hits, and the ways in which this process could change for the better. The changing world we live in makes predicting outbreaks a challenge, but each one teaches us something new about how to understand and to respond to the next.

To find out more about our conversations with Dr. Goldstein and Dr. Van Rompay, you can read their extended interviews here:

Continuing the Conversation: Dr. Tracey Goldstein on One Health, Bats, and Looking Ahead
Continuing the Conversation: Dr. Koen Van Rompay on Vaccines and Animal Models

Please head to the Science Communication Lab’s website for more films like this along with educator resources, full video transcript, and most up to date content.

View Transcript on SCL Website →
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Speaker Bio

Tracey Goldstein

Tracey Goldstein

Tracey Goldstein is a Professor in the Department of Pathology, Immunology and Microbiology and Associate Director of the One Health Institute. Dr. Goldstein is Co-Principal Investigator and Pathogen Detection lead for PREDICT, a project of the USAID Emerging Pandemic Threats program. She oversees the One Health Institute Laboratory and the Marine Ecosystem Health Diagnostic and… Continue Reading

Koen Van Rompay

Tracey Goldstein

Koen Van Rompay is a veterinary researcher from Belgium, who completed his PhD at UC Davis. He is a Core Scientist in the Infectious Disease Unit at the California National Primate Research Center (CNPRC) at UC Davis. Dr. Van Rompay’s expertise is in nonhuman primate models of viral infections, most notably HIV and Zika virus,… Continue Reading

More Talks in Human Disease

Related Resources

Scientific Papers Referenced:

Anthony, SJ et al. (2017). Global patterns in coronavirus diversity. Virus Evolution, 3(1).

Chen, N et al. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet, 395(10223), 507-513.

Holshue, ML et al. (2020). First case of 2019 novel coronavirus in the United States. New England Journal of Medicine.

Lauer, SA et al. (2020). The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Annals of internal medicine.

Xu, X et al. (2020). Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ, 368.

Credits

  • Kevin McLean (iBiology): Producer
  • Isabel Ponte (The Edit Center): Editor
  • Adam Bolt (The Edit Center): Editor
  • Chris George: Design and Graphics
  • Maggie Hubbard: Design and Graphics
  • Jeremy Poulos (UC Davis Academic Technology Services): Videographer
  • Images and Footage from NSF, NIH, UC Davis School of Veterinary Medicine, California National Primate Research Center, Nigel Walker
  • Music from APM Music (“Idea Space”), Jingle Punks (“Needle Drop”), and iSpy Music

Reader Interactions

Comments

  1. Sharon says

    This is very informative but the music playing over the dialogue is really loud and jarring and distracting. It was hard for me to hear what the scientists were saying at times because of the “background” music, which was more like foreground music. If the music track were turned down a bit it would be much better.

    Reply

  2. Phumlani Lonnie Mkhize says

    We do know for a fact that some bacteria can kill viruses. And also we do know the mechanism of how. I am talking about bacteria that add methylation groups in their nucleotide genome and when a virus inserts it in a non-methylated genome, the virus uses restriction enzymes to cut and remove all foreign GENOME. We know this works. By reducing the viral genome into individual nucleotides, the bacterial effectively kills the Virus. All  have heard to this point is targeting Viral Proteins as a way to contain the Virus. Inhibiting the behavior of viral proteins i.e. interfere with one of the pathways of viral replication is the standard way. And that is the reason HIV remains uncured. My question is this: Why is the IDEA of target Viral RNA or DNA genome such an elusive concept. It is never discussed. And I have listened to a lot of these lectures and I took classes at Columbia University. One Professor even had the nerve to say “You cannot kill a virus because it is NOT alive”

    I guess you get my point. We need a change in paradigm. In undergraduate, graduate and postgraduate we are taught about Enzyme inhibition. That is all. And we get jobs in pharmaceutical companies and we apply our classroom knowledge and we look for Proteins/Enzymes in Pathogens to target because we were taught that is how you fight pathogens.

    We have to start creating pharmaceutical products with endonucleases restriction enzymes based on the recognition sites of the VIRAL RNA Genome and the moment the CoronaVirus enters the cytoplasm  our drug(encoded with restriction enzyme) bind those recognition site and cut the Coronavirus into pieces of nucleotides. That will be the end of the Coronavirus and thank God it 

    In we can start by a culture of known bacteria that uses endonucleases and introduce the Coranvirus in the media with bacteria. If the bacteria kills Coronavirus we are two stepS away from the CURE. We just have to adapt or modify that enzyme the bacteria uses for the human body. And last but NOT least the goal IS NEVER TO GET OUR IMMUNE SYSTEM involved in this fight because our immune system is so underdeveloped and backward that it kills everything including the infected cells. We need these cells in the lung to do their job. Killing the host cell in this case is NOT the best route.  I always make an example of the Osama Bin Laden raid in Pakistan. The immune system(Pakistan Police and Security) were unaware that the Special Forces had entered the compound looking for a bad guy. After killing the bad guy(CoronaVirus) they left Pakistan without the knowledge of the Pakistan Police. You want the drug to enter Alveoli cells and remove or kill the RNA Genome(Coronavirus) and leave Alveoli  cells without the knowledge of the immune system. We need Alveoli cells to exchange oxygen/carbon dioxide. Killing these cells has serious consequences on the body maintaining homeostasis.
    Please provide feedback.
    Thanks
    Phumlani Lonnie Mkhize

    Reply

    • Shay says

      Greetings Phumlani. Are you still alive and well, and have you made any more progress on this idea? I will admit I’m not very educated on the topic, but your comment made sense to me and it’s a shame no one else is talking about it. I am going to show this to my Biology teacher and see what they have to say on the topic. I may come back and post their opinion to help answer your question. Until then, best of luck to you.

      Reply

  4. Candy DeBerry says

    I agree that the music is distracting. It is unnecessary.
    Overall, this is a good, short introduction which I am planning to use in my Cell Biology class this fall. Due to the pandemic, my lab will be all online and formatted to introduce undergraduates to the process of scientific publication and how to read and present primary literature. The topic will be the cell biology of cells infected with SARS-CoV-2.

    Reply

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