Avi Ma’ayan, PhD
As the public turns its attention to vaccine development in the hope of ending the COVID-19 pandemic, equally important work is taking place in the area of drug repurposing—identifying drugs already approved for other diseases that may also be effective for COVID-19. Repurposed drugs offer a safe and relatively quick and inexpensive treatment route.
At the Icahn School of Medicine at Mount Sinai, a team of researchers led by Avi Ma’ayan, PhD, Director of the Mount Sinai Center for Bioinformatics and Professor of Pharmacological Sciences, is investigating drugs with the most potential. To that end, they created the COVID-19 Drug and Gene Set Library, a crowdsourced database and website that consolidates information from multiple labs around the world that performed in vitro COVID-19 drug screens. These in vitro tests are performed in a petri dish, which is the first stage in drug discovery, before the drugs are tested in animal models and then in human clinical trials. The website is available to all scientists who want to compare drug screen “hits,” and has drawn 2,000 viewers since it was launched in April.
“Drugs are just as important as vaccines and offer a solution for dealing with this pandemic,” says Dr. Ma’ayan. “The hope is that we’ll find a drug, or a combination of drugs, that people can take after they’re infected with the virus to block the virus from spreading and enable them to mount an effective immune response.” After all, he adds, not everyone may be eligible to receive a vaccine, based on their health profile, and even with a vaccine there will be people who get COVID-19 and need treatment.
Venn diagram shows some overlap in a set of drugs relevant to COVID-19 research
In September, the journal Patterns, a Cell Press publication, published an article that described the Ma’ayan Laboratory’s work on the project. The article described the lab’s machine learning approach, which explored approximately 200 “positive hit” drugs that were identified as inhibiting the SARS-CoV-2 virus, which causes COVID-19, from infecting human cells in vitro. Based on the shared biological and chemical properties of these drugs, the machine-learning model prioritized these drugs further and predicted additional compounds with similar properties.
“When you start synthesizing data from multiple studies, you look for consistency and seek to identify interesting mechanisms,” he says. “We want to understand the mechanism of action of those drugs. Why do they work? What are the pathways they affect? What are the targets of those drugs so we can better understand the lifecycle of the virus?” Currently, the laboratory led by Benjamin tenOever, PhD, Director of the Virus Engineering Center for Therapeutics and Research at the Icahn School of Medicine at Mount Sinai, is conducting experiments to further explore some of these questions in collaboration with Dr. Ma’ayan.
According to Dr. Ma’ayan, the COVID-19 Drug and Gene Set Library organizes information in a way that can be clearly summarized and reused at a crucial time in COVID-19 research, when time is of the essence. The library allows the scientific community to work together toward a cure and avoid promoting drugs that are not fully validated, which happened last spring with hydroxychloroquine.
“The website that we built is supposed to be unbiased,” he says, “and it looks at evidence in a way that offers consistency across the studies, where the right answer comes up in a more distributed, democratic way.”
When considering promising drugs Dr. Ma’ayan points to the example of HIV, a virus for which there is no vaccine, but many combinations of drugs that effectively keep the viral load very low and prevent new infections. These drug “cocktails” have helped improve the lives of many people around the world. “There are fewer people dying from HIV because of these drugs,” he says. “It’s not guaranteed we’ll have a vaccine for COVID-19 that’s 100 percent effective or even 50 percent effective, and there are people who aren’t going to be able to receive the vaccine. If people get sick from COVID-19 and you have drugs that can treat them, you could turn it into a disease that more people can recover from.”