UF Scripps experts in virology, drug discovery and RNA biology to collaborate on nationwide effort to develop new medications
Multiple scientists from UF Scripps Biomedical Research will join a massive federal effort to develop antiviral drugs to treat the pandemic coronavirus and other viral threats.
Announcing its $577 million effort to stock the nation’s medicine chest with new treatments for dangerous viral diseases, the National Institute of Allergy and Infectious Disease announced last week that it is establishing nine multi-institution centers focused on developing new medications to address the ongoing COVID-19 crisis, and to treat other viruses with pandemic potential.
Seven UF Scripps scientists plus an engineer will contribute to three of those centers. The federal agency calls the groups “Antiviral Drug Discovery Centers for Pathogens of Pandemic Concern,” or AViDD. The AViDD grant awards to UF Scripps-directed projects and scientific core services could total more than $15 million over the next three to five years.
The awards highlight the institute’s unique strengths, which include rapid drug screening via robotics, RNA drug discovery, medicinal chemistry, pharmacology and virology, said Patrick Griffin, Ph.D., scientific director of UF Scripps Biomedical Research.
“Our faculty are global leaders in their respective fields. When the SARS-CoV-2 threat emerged, these scientists and their teams mobilized to help in the fight against the virus,” Griffin said. “With the support of these grants, UF Scripps scientists can continue to use their talents to benefit human health and help protect people from this and other pandemic viruses.”
UF Scripps scientists will join AViDD groups with significant expertise in virology and drug development. The first group, the Midwest AViDD Center, is co-directed by Reuben Harris, Ph.D., and Fang Li, Ph.D., professors at the University of Minnesota Twin Cities. Harris is also a professor and chair at the University of Texas Health San Antonio and an investigator with the Howard Hughes Medical Institute.
The second, the Center for Antiviral Medicines & Pandemic Preparedness, is led by virologist Sumit Chanda, Ph.D., a professor of immunology and microbiology at Scripps Research and its drug-discovery arm, Calibr.
The third, named Development of Outpatient Antiviral Cocktails Against SARS-CoV-2 and Other Potential Pandemic RNA Viruses, is led by Jeffrey Glenn, M.D., Ph.D., professor of microbiology and immunology at the Stanford University School of Medicine.
The Midwest AViDD Center includes 40 scientists at 16 sites. The scientists will study multiple steps in how the viruses enter cells, make copies of themselves, then escape to infect new cells.
The UF Scripps High-Throughput Molecular Screening team will work to rapidly screen UF Scripps’ massive compound collections for drugs that disrupt many steps in the viral life cycle.
Medicinal chemists and pharmacologists will help the team assess how candidate compounds are absorbed and whether they might have side effects that need to be improved before they move toward clinical trials. Another important aspect of antiviral drug development is to understand and limit the potential for the emergence of drug treatment resistance. UF Scripps scientist Choe will oversee that effort.
“My lab will do all experiments assessing escape potential of various viruses from those identified inhibitors,” Choe said.
Working with the Center for Antiviral Medicines & Pandemic Preparedness is Farzan, chair of the UF Scripps Department of Immunology and Microbiology, virologist Choe and chemist Matthew D. Disney, Ph.D., who chairs the UF Scripps Department of Chemistry. Farzan and Choe’s labs will work to find new drugs to block the entry of SARS-CoV-2 into cells.
Disney, meanwhile, will focus on discovering potential medications that disrupt or degrade viral RNA within cells to fight the pandemic coronavirus. Disney will also work on a project to drug certain targets with the Stanford-based group.
NIAID said the awards are part of an intensive research program designed to speed development of therapeutics for COVID-19, called the Antiviral Program for Pandemics.
As the AViDD awardees identify new drug candidates, the most promising ones will enter preclinical development, in collaboration with industry partners, NIAID said in its news release.
“The COVID-19 pandemic has highlighted the need for new antiviral drugs, especially those that could easily be taken by patients at home while their symptoms are still mild,” said NIAID Director Anthony S. Fauci, M.D. “Decades of prior research on the structure and vulnerabilities of coronaviruses greatly accelerated our response to the COVID-19 pandemic, and we hope that similar research focused on antivirals will better prepare us for the next pandemic.”
Seven UF Scripps Biomedical Research scientists and an engineer will oversee research programs or core scientific functions as members of three of NIAID’s AViDD groups. They are:
Midwest AViDD Center
Louis Scampavia, Ph.D., and Timothy Spicer, Ph.D., plus robotics engineer Pierre Baillargeon, will collaborate with others to rapidly screen UF Scripps’ massive compound collections for drugs that disrupt many steps in the viruses’ life cycle at the UF Scripps High-Throughput Molecular Screening center.
Thomas Bannister, Ph.D. will oversee the medicinal chemistry team at three sites, including at UF Scripps, supporting all projects. After screening and computational studies identify a candidate molecule, his group studies how these potential drugs interact with their target and then refine and optimize the compounds for effectiveness and safety.
“The objective is to find new classes of antiviral drugs with the potential to curb future epidemics before they can become widespread,” Bannister said.
In addition to leading medicinal chemistry efforts overall, Bannister will help lead one of the five subprojects, a team focused on targeting little-studied enzymes called helicases, which are essential for viruses to make copies of themselves.
Michael Cameron, Ph.D., a pharmacologist, will help the team assess how candidate compounds are absorbed, get to their site of action, and identify side effects or other drawbacks that need to be improved in the drug candidate before it should move further along toward clinical trials.
Center for Antiviral Medicines and Pandemic Preparedness
Farzan and Choe’s labs will work to find drugs to block the entry of SARS-CoV-2 into cells. They discovered the original cell receptor that the first SARS virus uses to infect. The pandemic coronavirus uses that same receptor.
Disney has developed a chemical tool that recruits cells’ own recycling system to disease-causing RNA targets, literally dissolving them with degradation enzymes. He will work on potential drug strategies against several RNA targets within the SARS-CoV-2 genome.
Development of Outpatient Antiviral Cocktails Against SARS-CoV-2 and Other Potential Pandemic RNA Viruses
Disney and his team will pursue additional viral RNA drug targets.
For more information about the AViDD grants, read the NIAID news release here.
For more information about UF Scripps Biomedical Research, visit https://scripps.ufl.edu