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Full Interview: Finding Powerful Antibodies to Fight COVID-19 with David Ho

6/2/2020

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By: Hannah Lin (CC '23)

Picture
David Ho, MD, is the Clyde '56 and Helen Wu Professor of Medicine and the director of the Aaron Diamond AIDS Research Center (ADARC) at Columbia University.



​Could you describe your COVID-19 research at the moment?

We have multiple projects going on in the lab. The biggest effort revolves around isolating monoclonal antibodies from patients who have been infected by SARS-CoV-2, or COVID. As you know, once infected, people mount an antibody response directed to the virus, and we are trying to find special patients whose blood contains very powerful antibodies that could kill SARS-CoV-2. What we’ve done is screen about 40-some patients; we took their blood, looked at the virus neutralizing activity of the blood, and focused on those with the most potent responses. We’ve been working very hard for the last couple months on 5 cases in particular, and we have been able to pull out lots of very potent antibodies that could kill SARS-CoV-2. We’ve been characterizing that, and I think we’ve been pretty excited about our results because we have found some antibodies that have never been described and are also very powerful ones. We’re characterizing them and also trying to figure out the structure of how the antibodies bind to the important part of the virus. That’s our first project. 

We also have a project that’s focused on developing drugs for SARS-CoV-2 by targeting an enzyme of the virus called protease. Protease is a chemical scissor that is required to cut the viral proteins from big chunks to small pieces, and if you find a drug that can gum up that chemical scissor, the virus can no longer replicate and therefore would be blocked. We’re busy looking at that, and we have a few chemical compounds that could do so, but not at very high activity at this point. We need to continue to work with chemists to synthesize what we call analogs, or related compounds, to see if any one of them will exhibit greater activity against the virus. This is an iterated process that we have to go through, and I suspect it’s going to take a while to get a compound that’s active in the laboratory to a drug that could potentially work in people. Those are the two major projects in the lab. 

We also have another project that is trying to develop rapid tests, so we can quickly measure whether someone has the infection or not by taking, say, a saliva sample and putting it to test, and in about 10-15 minutes, you can tell whether someone has the virus in saliva or not. That effort is also ongoing. Lastly, we have a project focused on how the virus or its viral proteins could be triggering a bunch of immunological cascades—how that triggers the immune system to do damage to various organs—going from the lung to the heart to the kidneys to the liver, and even to the nervous system. It’s what we call pathogenesis studies, and we have a project focused on that as well. Those are the principal activities related to this pandemic that my laboratory is undertaking.


Have you faced any setbacks in your research thus far?

In this sort of research, each day we have our setbacks. Certain experiments don’t work and you waste a day. In general, I would say we have not had major setbacks so far. Everybody’s working 24/7. It’s all hands on deck, and the progress we have made in the last 2-3 months would rival progress that a laboratory would normally make in 2-3 years. It’s rather remarkable the speed with which research is being conducted. Not just in my lab, but in many labs throughout the world because of this pandemic.


Is your team still keeping prior projects going, and how are you managing both?

No, we’ve been asked to only address the pandemic. Existing or prior projects are all put on hold, so only those working on COVID have been working. Our HIV research has essentially halted, although starting next week, some of it might kickstart once again. 


You’ve been in this field researching for decades now; has there been anything particularly in your COVID-19 research that has surprised you at all?

I’m pleasantly surprised by the way the scientific community has mobilized to an extent that’s unprecedented. The collaborative spirit is also a very, very pleasant surprise. People send us reagents and we send others reagents without even thinking about it, just doing it, helping each other out as quickly as possible by exchanging information. We’ve been impressed by the amount of scientific funding also—from the government, from foundations and philanthropists. There’s quite a bit of funding pouring in. All of those are very positive.


That reminds me of an article I saw where you talked about how the funding for SARS research trickled off, and that hindered progress for COVID-19 research now. Also from that article, developing solutions that may be more permanent has been a focus of your group in regard to treating potential viruses. Can you talk a bit about why that is one of your important goals and why it is so significant to look ahead?

We obviously learned a lesson: that if we had continued the research on SARS, we would be way ahead today. A lot of research on SARS came to a stop, and that’s part of the reason why we’re struggling to deal with this pandemic. Just thinking about coronaviruses, we know these viruses have relatives in various animal species, particularly in bat populations. This is the third epidemic, or pandemic, in the last 20 years due to a coronavirus. Surely, others will emerge, so we need to broadly prepare for those we know about that exist in animal species. We are obviously trying to fix the current pandemic, but in the back of our minds, we are seeking solutions that could be broadened to cover other related viruses. 


Are there any common misconceptions about COVID-19 that you want to set straight for the public?

I think there’s a lot of misinformation out there being spread by various people, from some average Joe on the street all the way to the White House. There are many misconceptions in regular media and also in conversations between people. I think this pandemic is a real threat; one should not trivialize it. Most people don’t, but there’s a segment of society that has been believing that this isn’t such a big deal, and that’s because they haven’t seen the carnage or devastation that we see in the medical center here. While pausing at home is difficult, it is the proper thing to do to bring this outbreak under control. Fortunately, in New York, I think we’ve picked up well over the last couple months. But throughout the country, there are many regions that are not doing all that well, and yet they’re still opening up. As a specialist in this area, it frightens me a great deal. I fear for what may come in the coming months. 


For some optimism: a lot of people look to you for inspiration because of all the important work you’ve done; have you yourself been inspired by anyone or anything during this pandemic, not necessarily in scientific research, but in general?

Of course, we’re all inspired by the frontline healthcare workers, who put their own bodies at risk to help take care of the sick and dying, and in great numbers. It’s pretty admirable. I used to be a physician who sees patients, but I haven’t been doing that for some time, so that’s inspiring, and it’s prompted me and my colleagues in the laboratory to try to match their effort. We realize they’re taking care of the patients now, but we hope to develop solutions that will help take care of the patients in the future. 

​
What is your perspective on the future, both in terms of your research and the impacts of COVID-19 on science and society at large?

This pandemic is here to stay for a while, and our lives are going to be changed for a long time. We need to take it seriously, and everyone should do everything possible to mitigate transmission of this virus to buy scientists some time to come up with solutions. I think there’s a misconception that solutions are very quick and that in the course of a few months, we will have a vaccine or a drug. I’m quite confident in the success that we will ultimately reach; however, it will take time. It will certainly take more than a year, perhaps up to two years, before anything really, really useful will come out. 

On the science side, I think we’re getting a real boost, particularly in virus research. It’s a reminder of how important this work is. We spend billions and trillions on defense against a foreign power, and yet we spend relatively little against a foe like this kind of virus; look at the devastation that has caused. It’s teaching us a lot about our priorities. This is nothing new; scientists have been saying a pandemic will come; it’s only a matter of when, not if. Yet the leadership of our country and many other countries simply don’t believe that. Hopefully, this is a wake up call for everyone.
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