Four years after the launch of Forethought: The RTI $5M+ Research Collaboration Challenge, the Rapidly Emerging Antiviral Drug Development Initiative (READDI) is advancing two drug discovery campaigns toward investigational new drug (IND) status. The initiative aims to develop new antiviral drugs for future pandemics.
In its main campaign, READDI has validated a target and identified a promising compound, which medicinal chemists are optimizing to be more potent, specific, and non-toxic. This drug is intended for diseases caused by coronaviruses. A second campaign is underway for a backup target that may have broader applications across different virus families.
The Forethought Challenge began in 2021 with the aim of encouraging bold research proposals through regional collaboration in North Carolina. READDI formed a consortium including virologists from the University of North Carolina at Chapel Hill and Duke University, a computational biologist from UNC-Chapel Hill, a drug-screening expert from North Carolina Central University, and RTI’s own medicinal chemists and pharmacologists.
READDI focuses on developing small-molecule antiviral medicines that can work against entire virus families. These broad-spectrum drugs are designed to prevent viruses from infecting and replicating in cells, which could reduce severe illness and slow viral spread.
For this project, READDI concentrated on coronaviruses—responsible for outbreaks such as SARS in 2003, MERS in 2013, and COVID-19 in 2020—by targeting host-cell proteins necessary for viral replication rather than viral components themselves. Host-directed antivirals may also help limit drug resistance.
The team used expertise across several fields to narrow down potential targets among thousands of human cell proteins. Virologists and computational biologists developed systems to analyze large datasets and prioritize possible targets.
“We took a first-principles approach,” says virologist and READDI co-founder Dr. Nat Moorman, associate professor at the UNC School of Medicine. “We considered all things that had been implicated at one level or another in disease caused by coronaviruses — basically everything that could be measured in a cell at a genome-wide level.”
Once targets were prioritized, RTI researchers selected the most promising one using medicinal chemistry and pharmacology skills before launching a program to develop a lead compound.
“By utilizing our expertise in small molecule drug discovery and pharmacology, we have made great strides towards developing novel molecules to target these proteins by taking a considered team approach,” says Scott Runyon, director of organic and medicinal chemistry at RTI.
The group’s multidisciplinary background has contributed to what it describes as an intentional strategy. “During the pandemic, a lot of researchers simply tested existing compounds or tried to repurpose current antiviral drugs, hoping to get lucky,” Moorman says. Many of those efforts failed. “We have been more intentional, working through target hypothesis and validation.”
Moorman notes that their next goal is getting a molecule ready for clinical trials with hopes for an effective broad-spectrum coronavirus treatment covering both known viruses and those yet undiscovered.
Forethought: The RTI $5M+ Research Collaboration Challenge was created by RTI International together with its Board of Governors University Research Collaboration Committee (URCC) as part of ongoing investments into university partnerships meant to stimulate change within the Research Triangle region’s research community.
READDI received support from RTI along with initial funding from UNC-Chapel Hill and the NC Collaboratory before securing additional funds from agencies such as the National Institutes of Health, U.S. Department of Defense, and North Carolina General Assembly.
“Developing effective broad-spectrum antivirals is a challenge bigger than any single lab, institution, or company,” says READDI CEO James Rosen. “We are grateful for RTI’s foresight and funding in launching this important collective effort.”
