Image: The compound UMB18 (multi-color) binds to the 3D structure of SKI protein complex shown in silver (Photo courtesy of UMSOM)
Researchers at the University of Maryland School of Medicine (UMSOM Baltimore, MD, USA) 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. 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.
The researchers 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). 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.
“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.”
“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.
University of Maryland School of Medicine