ReFRAMing Research: How new technology could reveal a treatment for COVID-19
In response to the COVID-19 outbreak, the Bill & Melinda Gates Foundation will provide up to $100 million to improve detection, isolation and treatment efforts; protect at-risk populations in Africa and South Asia; and accelerate the development of vaccines, drugs and diagnostics. We sat down with Ken Duncan, lead of the Gates Foundation’s Discovery & Translational Sciences team’s drug discovery efforts, to discuss how the team is harnessing existing drugs and research, as well as advancements in robotics to rapidly accelerate drug and vaccine development.
Q: When it comes to COVID-19, we know this virus is moving very quickly. R&D, though, can be slow, especially when it comes to developing vaccines and antivirals. So, what value is there in focusing on R&D for this pandemic?
A: Well, there are few important things to understand.
The first is that our R&D efforts are not only focused on developing new drugs, but also on repurposing existing drugs which are already registered for other uses. Many drugs have already been developed to treat infections caused by other viruses. Ideally, we can use those if any are sufficiently active against COVID-19. Some might be in the late stage of development, and others might be on the shelves of pharmacies already.
We also have to think about how we’d use a drug. The current front-runner to treat the infection, remdesivir, has to be administered intravenously, so you're only going to be able to use it in hospital settings to treat people who are already seriously ill. You couldn't use it to protect a lot of people at once.
The good news, though, is that we also have ways of quickly testing and developing new antivirals.
Q: What are those?
A: Unlike even a few years ago, we now have access to an incredible new tool called the ReFRAME Collection. It’s a collection of thousands of compounds that have already been tested for safety. And we can rapidly evaluate these compounds to see if they are active against COVID-19. We’ve only had access to this tool for about 3 years, which means it’s just beginning to realize its potential.
Q: How does that process work exactly? Are you looking through this library of molecules and discovering whether something is useful for treating COVID-19?
A: There are basically two steps we are involved in right now. As a first step, we’re testing about a hundred different registered drugs that are most likely to be active against the virus.
Step two is utilizing the ReFRAME Collection—which has 13,000 compounds—to search more comprehensively. Thanks to advances in robotics, we can do this at a high rate of speed. You expose the virus to these compounds and collect readouts on which compounds are effective in stopping them.
Once a compound appears promising, we’ll move on to testing it in vivo in mice which have been “humanized,” or engineered to have the human ACE2 receptor, which is the protein that a respiratory virus like COVID-19 binds to when it goes into the lungs. And then we look to see if any of those humanized mice survive the viral infection.
Q: Is the next phase after that humans?
A: Yes. And unlike the normal timeline of drug discovery, which typically takes at least two years from discovery to testing in patients—in this case, we could be into human testing within a few weeks.
About the Interviewee
Ken Duncan leads the Discovery & Translational Sciences team’s drug discovery efforts.
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