Mount Sinai Awarded Up to $11.8 Million From ARPA-H to Close the Doors in Human Cells That Viruses Exploit to Infect, Replicate, and Spread
Credit: Mount Sinai Health System. This graphic was created with the help of AI.
Researchers from the Department of Microbiology at the Icahn School of Medicine at Mount Sinai have been awarded up to $11.8 million from the Advanced Research Projects Agency for Health (ARPA-H)to identify and block the critical points inside our cells—the “doors”—that viruses must exploit to infect, replicate, evade defenses, and spread. ARPA-H is a federal funding agency that accelerates better health outcomes for everyone by supporting the development of high-impact solutions to society's most challenging health problems.
The Closing the Doors to All Pathogens Through Integrated Digital Experiments (DOORs) project will map these critical doors in human cells by systematically comparing viruses that can infect humans with closely related ones that cannot, thereby pinpointing which doors are truly essential for spillover and disease.
“Previous research conducted by members of our department and our team have already successfully described a map for influenza virus,” said Gustavo Palacios, PhD, Professor of Microbiology at the Icahn School of Medicine at Mount Sinai and Principal Investigator of the DOORs project.
“The funding from ARPA-H will enable us to create a comprehensive roadmap to describe all pathogen-host interactions that can be applied to all pathogens. By mapping and modeling these conserved interactions and identifying the viral ‘keys’ that unlock them, we will provide the foundation for closing these doors through the development of broad-spectrum antivirals based on host targets,” said Adolfo García-Sastre, PhD, Director of Mount Sinai’s Global Health and Emerging Pathogens Institute, where the work will be based, and co-investigator on the award.
The COVID-19 pandemic showed how unprepared we are when a new pathogen emerges. Current approaches often mean starting from scratch against each virus. The DOORs program’s systematic approach—powered by multi-omics, functional genetics, evolutionary biology, and artificial intelligence—will shift the focus from chasing each new virus to building a reusable, generalizable platform for broad-spectrum antivirals.
Credit: Mount Sinai Health System. This graphic was created with the help of AI.
“The DOORs project is the first project designed to apply this concept across multiple viral families and not just a single pathogen,” said Dr. Palacios. “If successful, this work could dramatically shorten the timeline for developing antiviral therapies. Instead of waiting for the next outbreak, we will already have validated targets and host-directed drugs that block entire classes of viruses. This could change how we respond to outbreaks, reduce reliance on single-use ‘silver bullet’ drugs, and ultimately, strengthen our global biodefense.”
In addition to creating a comprehensive computational map of pathogen-host interactions, the DOORs project aims to uncover the best drug targets for an entire family of pathogens. They will also test approved therapies and discover new ones through computer modeling.
“We are profoundly grateful to ARPA-H for selecting this team to lead this critical research that is designed to better protect us all from the array of pathogens that can threaten our health and well-being,” said Eric J. Nestler,MD, PhD, Interim Dean and Nash Family Professor of Neuroscience at the Icahn School of Medicine at Mount Sinai; Executive Vice President and Chief Scientific Officer of the Mount Sinai Health System. “This is the first ARPA-H awarded project to have its primary home at Mount Sinai, which brings us great pride as it is a recognition of the Icahn School of Medicine’s pre-eminence as a leading biomedical research institution.”
“The vision for DOORs is to protect U.S. national security from emerging biological threats with an integrated, digital experimental workflow that closes the loop for detecting, understanding and responding to infectious diseases while making these activities commercially viable through host-based therapeutic discovery,” concluded Dr. Palacios. “The long history and depth of experience of our esteemed microbiology faculty here at Mount Sinai makes us uniquely poised to lead this effort. We are extremely grateful to ARPA-H for their generous commitment to help us advance this critical scientific work.”
“Dr. Palacios’ collaborative nature and his unique background in virology and pandemic preparedness have made him an integral member of the Department of Microbiology at Mount Sinai since he joined us three years ago,” said Ana Fernandez-Sesma, PhD, Chair of Microbiology at the Icahn School of Medicine. “Under his leadership, this multi-disciplinary team is poised to accomplish their goal of closing the doors to all pathogens.”
Other institutions that will be involved in this work include the University of California, San Francisco; Calibr-Skaggs Institute for Innovative Medicines, Scripps Research; and Columbia University.
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