Combing through old drugs to find new ones for COVID-19
Developing a new drug from scratch takes many years, but as the COVID-19 pandemic continues to kill thousands of people around the world each day, some therapeutics researchers are trying a faster way to find a COVID-19 drug. Scientists, including those at the Broad Institute of MIT and Harvard, are testing existing drugs that are already proven safe in humans, to see whether they can be repurposed to treat COVID-19 patients.
The Broad’s Center for the Development of Therapeutics (CDoT) is a part of this effort. It is making copies of its Drug Repurposing Hub — a collection of nearly 7,000 compounds that are either FDA-approved or proven safe in clinical trials — and sharing them with collaborators in Boston and around the world to help them hunt for existing compounds that might prove effective against COVID-19.
Drug repurposing works. The FDA recently granted emergency use authorization for a drug called remdesivir for COVID-19. The compound was originally developed for hepatitis C and was tested in humans in 2015 and 2016 as a possible treatment for Ebola before showing benefits for COVID-19 patients. (The Drug Repurposing Hub was not involved in this effort.)
We spoke with institute scientist Florence Wagner, director of medicinal chemistry in CDoT and the Stanley Center for Psychiatric Research, to learn more about how she and her team are working with other research groups on both near- and long-term projects. We also spoke about how drug repurposing, as the first phase of COVID-19 drug development, holds tremendous potential for rapid clinical impact.
Q. What is the promise of drug repurposing for COVID-19?
A. For COVID-19, there is an urgency to find pharmaceutical compounds that could help treat symptoms or decrease the viral load in affected patients. That need is acute; patients are dying right now. One of the fastest things scientists could do that could have a significant impact is to test those drugs that are already on the market. If we find positive hits in drug screens, doctors could possibly prescribe them, as they are already FDA-approved and shown to be safe.
CDoT's Anita Vrcic in front of stacks of Repurposing Hub assay-ready plates (Photo credit: Anita Vrcic)
Q. How is CDoT supporting COVID-19 therapeutics research?
A. The compounds in our Repurposing Library are FDA-approved, or clinically tested but not yet FDA-approved, or are optimized probe compounds, which are highly optimized against a number of specific targets and usually very potent.
When research activities onsite at Broad were winding down in March, we at CDoT were responding to requests from collaborators and labs around the world for our Repurposing Library. In fact, Anita Vrcic, team leader of CDoT’s compound management facility, went in and plated 7,000 compounds, by herself, onto assay-ready plates so that they could be shipped to our collaborators studying COVID-19. So far, we have responded to requests from multiple labs in the Boston area, around the country, and also outside the country.
In addition, we’re serving as a centralized compound management function for the Massachusetts Consortium on Pathogen Readiness, a multi-institutional effort that is investing in the research and infrastructure needed to address the current pandemic. This means that we will receive, process, and ship samples of compounds to be tested in COVID-19 related screens.
Q. What happens after you send the compounds to research groups?
A. Once our collaborators have received assay-ready plates, they can immediately test the entire collection in their biological assays. When they finish their studies with the library of 7,000 compounds, they share the data with us, and we will make the data openly available to the research community via our website — this is work in progress. Other researchers can download these publicly accessible datasets from our website, do their analysis, and even compare with their own data from other drug screening experiments, which may have been conducted with a different system or cell type.
There is also going to be an effort to aggregate and visualize the data on a new website we plan on launching in the next few months.
Q. How is CDoT collaborating with other Boston-area researchers and labs? How did these collaborations start?
A. It all stemmed from the Massachusetts Consortium on Pathogen Readiness. Mark Namchuk from Harvard Medical School, who is co-leading the therapeutics efforts of this consortium, first connected with Deborah Hung (core institute member at Broad), who put him in touch with us at CDoT.
So one of our first collaborations started with Mark and Robert Davey at Boston University’s National Emerging Infectious Diseases Laboratories. In fact, our first shipment of the Repurposing Library went to Davey’s Biosafety Level 4 lab, where they are testing thousands of drugs against lab cultures of cells infected with SARS-CoV-2, to rapidly detect which drugs are most effective at halting or reducing infection.
In addition to testing FDA-approved repurposing drugs, Robert, Mark, and I have also partnered with industry collaborators to test proprietary compounds. Our industry collaborators ship these compounds to CDoT’s compound management facility. We process the compounds, complete quality control steps, plate them onto assay-ready plates, and send the plates to Robert’s lab for testing against the virus.
Q. Beyond conducting drug-screens with the Repurposing Library, what does the next phase of COVID-19 therapeutics research look like?
A. We are thinking long-term, beyond this pandemic. This is not the first coronavirus. We had SARS and MERS in the past. It seems like it's coming every seven years. The prediction is that we are going to have another virus coming eventually.
One thing we are thinking about is the potential to create “pan-COVID inhibitors,” which would work against more than one type of coronavirus. Those kinds of drug discovery projects will take longer — many years. If successful, these compounds can be used as prophylactics when there is an emergence of a new virus, where physicians can give that medication to patients and try to contain the infection as much as possible. And the hope will be to create compounds that would work against any coronavirus, not just SARS-CoV-2. We have to start thinking beyond this pandemic.