What the experts are saying: biggest takeaways from our ongoing COVID-19 conversations

Since the COVID-19 pandemic began, the Buck has been gathering evidence-based opinions and information from top researchers and thinkers about the science aimed at bringing it to an end. What are the biggest takeaways so far? How close are we to getting back to normal? Everyone, from molecular biologists and epidemiologists to clinicians and public health experts, has been remarkably consistent on a few key points. Don’t have time to listen to 11 hour-long conversations? No problem! We’ve assembled the highlights from these  webinars in a 4-part series.

Part 1

Science and research

Researchers have been working on understanding the virus and possible therapeutic approaches since January. Here is what we’ve learned so far:

What does the virus do?

Nevan Krogan, Director of the Quantitative Biosciences Institute at UCSF: So the virus, itself, is comprised of protein in RNA, okay? And it injects its RNA into our cells during the course of infection, and it forces our machinery to make about 30 different proteins. You know, there’s only 30 proteins, or probably less, associated with the virus, and there’s over 20,000 potential proteins in each one of our cells. So the virus cannot exist by itself. It can’t live. It needs our cells, our genes, our proteins, in order to live and replicate and infect our cells. So the way it does that is it hijacks and rewires our machinery, our proteins.

What do we need to know to stop it?

Melanie Ott, Director of the Gladstone Institute of Virology : So we currently are really doing these infections in the cell at a single level… we know all of the factors that are going up and all of the factors that are going down in a cell when it becomes infected, but also in a cell that sits next to the infected cell and does not become infected. And that cell is almost more important for us to study because we want to know what effectively is actually preventing the infection in this cell.

Robert Gallo, Co-founder & Director, Institute of Human Virology at the University of Maryland School of Medicine: You know, viruses, they’re not alive. They use us to replicate with a few genes of their own. So you have to have a clear understanding of the molecular biology of their cycle of replication. That came from molecular biology, from basic research, the kind of things that are done at the Buck.

Ugh, mutations!

MO: And so these random mutations can become very important in the long run. So, for example, when I say viruses can develop resistance against drugs relatively fast, especially if it’s a drug that targets a particular factor in the virus directly, because then these random mutations occur.

But, so far, it has not shown a very high mutagenic rate, and, also, it hasn’t shown a certain direction in where it’s going. This might change, as I said, if we put some selection pressure onto this virus in the form of growing immunity in the population, a vaccine, or potential therapeutics that might cause emergence of mutant strains.

RG: We know a lot more about mutations now, but not yet sure that I can tell you, ‘Yeah, there’s a strain. Let’s call it Strain B, and that’s doing this, that and the other.’ That’s still too early. But I think that might come maybe before summer ends that we’ll have that kind of information.

Warner Greene, Director of the Gladstone Center for HIV Cure Research: So it’s an RNA virus, and, by definition, the RNA viruses change more than DNA viruses. That said, SARS-CoV-2, and the coronaviruses, they all have this proofreading enzyme, which tends to correct a lot of the errors that are made. So they do not tend to mutate as much as, for example, HIV, or hepatitis C. So that’s good news for vaccine development, that the sequence, while modestly changing, is not radically changing all the time.

Host-oriented research could be the solution

NK: We’re trying to identify the human proteins that the virus needs to infect us and then let’s pharmacologically target those human proteins. And there’s advantages to that strategy. One, you know, we don’t mutate as fast as viruses. So one of the issues about having drugs that target viruses is that you get mutations, and then you get resistance... We and others have shown that viruses, even very distinct viruses, are targeting similar human proteins. They’re hijacking and rewiring them during the course of infection. So the logic would be if you could actually have a host-directed therapy for COVID-19, it would be more easily brought to bear for COVID-22, COVID-24, or even other viruses that we’re trying to combat, as well.

The Buck’s Role

Eric Verdin, President and CEO of the Buck Institute: And so Nevan and his colleagues were able to do this and to identify a large number of cellular proteins [that the virus interacts with]. And it turns out, quite interestingly, that many of these cellular proteins are proteins that we know at the Buck are involved in the aging process. 

This is where I think the history of the Buck in conducting research on aging is really incredibly important to this effort. 

RG: Support the Buck Institute, and make them work faster and harder because I’m 83 years old, you know, and that’s… it goes faster and faster, and we want them to understand the intricacies of the aging process in immunology.

So every time somebody 75 died, you know, you got some older people dying. Now, you can say there are a lot of old people in Northern Italy, and there are, but I think that’s really a telling thing. And I would think that the Buck Institute should figure that out. Not me.

John Newman, Assistant Professor at the Buck and Practicing Geriatrician: a lot of my colleagues at the Buck Institute and around the country have been very interested in this idea of inflammaging and how to improve the immune system of older adults for years now. And I hope that in the not too distant future, we’re going to have interventions to specifically help the immune systems of older people work better, so when the next virus comes, even if it’s not the, you know, SARS-CoV-2 coronavirus, it’s some other virus, we’ll have things that we can do to help.

NK: And it’s been a great pleasure interacting with Eric and a number of scientists at the Buck Institute. And, again, it’s a testament to, you know, the collaborative relationships that have been formed, you know, in the Bay Area around this. And the challenge now is to keep the momentum going, not just on COVID-19 but other diseases, as well.

The scientists are unanimous in their unity:

EV: Scientists sometimes collaborate, but also compete fiercely. What I have seen in the case of the COVID-19 and this coronavirus, it’s really the opposite. So I think everyone recognizes this is not a time for fierce competition. This is a time for collaboration and bringing a solution to the problem as fast as we can. And, in some way, it is a new way to do science. I find it incredibly refreshing. And I think it will change the way in which we work in the future, and, hopefully, this will be one of the good things that will come out of this pandemic.

Larry Brilliant, Chairman of Ending Pandemics: I can’t imagine a world in which we deal with a global threat without a global solution and global partnership. There are no walls, there’s no moats, any number of alligators or crocodiles in that moat is not going to protect you. It is in your best interest, oligarch, it is in your best interest, you know, billionaire, it’s in your best interest to make the world safe by a concerted global effort. We truly are all in this together. Anything less is unthinkable.

MO: But I think the big difference from the beginning of the AIDS epidemic and now is that we are doing science, really, in a different way today.  We are learning much faster, and we are… and we are sharing this knowledge much faster, and we’re also doing science in a different way today.

NK: . What we’ve seen is these silos have really been broken down. And I think as a scientific community, not just with us but around the world, we see how fast science can actually move and, you know, breaking down silos across different laboratories, across different institutions. And then also between academia and pharmaceutical companies. We’ve seen this as well with us and with other groups. And, for me, this has been really the most exciting part of this.

Kevin Tracey, President and CEO, Feinstein Institutes for Medical Research: We just saw some of the best kind of work that humans can do to help each other. Northwell, as you said, is 23 hospitals, 70,000 employees, hundreds of outpatient facilities and skilled nursing facilities. And in the early days of the response to this epidemic, these 70,000 people came together as one around an emergency. And the response was… frankly, it was awe-inspiring to be part of, and we’ve gotten through it quite well. 

WG: the one thing that’s been gratifying is to see the incredible scientific collaboration that has occurred. Scientists really working in ways that are not in their own self-interest, but in the interest of progress in the field. And that’s been very, very satisfying. So I’m impressed with the amazing focused effort that’s going on around the world. I don’t think we’ve ever seen science so squarely focused on a problem like this as we are seeing now, and it’s going to yield great fruits.

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Our next set of takeaways focuses on the overlap between public and personal health measures, including our best advice for upping your own immune protection from this and other infections.