November 13, 2020 | Deborah Kotz
The compound UMB18 (multi-color) binds to the 3D structure of SKI protein complex shown in silver.
Research Could Accelerate Efforts to Develop New Anti-Viral Drugs to Fight Flu, Ebola, and Novel Coronaviruses like COVID-19
Researchers at the University of Maryland School of Medicine (UMSOM) and School of Pharmacy (UMSOP) have discovered new drug compounds to potentially treat the novel coronavirus that causes COVID-19. The compounds disrupt the functioning of a protein complex inside human cells that the researchers discovered is critical for the replication and survival of coronaviruses. This finding could lead to the development of new broad-spectrum antiviral drugs that target viruses such as influenza, Ebola and coronaviruses, according to a new study published today in the Proceedings of the National Academy of Sciences (PNAS) journal.
The protein complex, called SKI complex, is a group of human proteins that regulates various aspects of the normal functioning of a cell. In the new study, the researchers discovered that this complex also plays a crucial role in helping a virus replicate its genetic material, called RNA, within the cells it infects.
“We determined that disrupting the SKI complex keeps the virus from copying itself, which essentially destroys it,” said study corresponding author Matthew Frieman, PhD, Associate Professor of Microbiology and Immunology at the UMSOM. “We also identified compounds that targeted the SKI complex, not only inhibiting coronaviruses but also influenza viruses and filoviruses, such as the one that causes Ebola.”
He and his colleagues from the School of Pharmacy’s Computer-Aided Drug Design Center and the Center for Biomolecular Therapeutics at the UMSOM used computer modeling to identify a binding site on the SKI complex and identified chemical compounds that could bind to this site. Subsequent experimental analysis showed these compounds to have antiviral activity against coronaviruses, influenza viruses, and filoviruses (such as Ebola). Researchers from the National Institute of Allergy and Infectious Diseases also participated in this study.
The study was funded by Emergent BioSolutions, a biopharmaceutical company based in Gaithersburg, MD. The further development of these compounds is funded by Aikido Pharma.
“These findings present an important first step in identifying potential new antivirals that could be used to treat a broad number of deadly infectious diseases,” said study lead author Stuart Weston, PhD, a research fellow at the UMSOM. Such drugs have the potential to treat infectious disease associated with future pandemics. Next steps include conducting animal studies to learn more about the safety and efficacy of these experimental compounds, which are not approved by the Food and Drug Administration.
In other research efforts funded by the federal government, Dr. Frieman and his team are rapidly testing hundreds of drugs, approved and marketed for other conditions, to see whether any can be repurposed to prevent or treat COVID-19.
“As we face a potentially long, hard winter with COVID-19, our researchers continue their sustained efforts to advance innovations,” said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "Basic research remains a vital part of this effort to leave us prepared for the next global pandemic.”
About the University of Maryland School of Medicine
Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 45 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has more than $563 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 student trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of nearly $6 billion and an economic impact more than $15 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu
Contact
Deborah Kotz
410-706-4255
dkotz@som.umaryland.edu
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