The Sudan virus, which is closely related to Ebola, has a 50% mortality rate but is not well understood in terms of its infection process in human cells. Currently, there are no approved treatments for it. To fill this significant gap in our preparedness for pandemics, researchers from the University of Minnesota and the Midwest Antiviral Drug Discovery (AViDD) Center have studied how this lethal virus connects to human cells.
The Sudan virus, a close relative of Ebola, has a fatality rate of 50% but remains poorly understood in terms of how it infects cells. Currently, no approved treatments exist. To address this critical gap in pandemic preparedness, researchers at the University of Minnesota and the Midwest Antiviral Drug Discovery (AViDD) Center investigated how this deadly virus attaches to human cells.
Similar to Ebola, the Sudan virus enters cells through its attachment to NPC1, a protein that plays a role in cholesterol transport. By utilizing cryo-electron microscopy, the researchers were able to clearly define how the Sudan virus interacts with the human NPC1 receptor. Their research identified that four significant amino acid differences between the receptor-binding proteins of Sudan and Ebola viruses allow the Sudan virus to bind to human NPC1 with nine times the strength of Ebola, potentially explaining its higher fatality rate.
Building on this revelation, the team also estimated the receptor-binding affinities of three other filoviruses that are closely related to Sudan and Ebola. They further explored how the Sudan virus connects to NPC1 receptors in bats, which are thought to be natural carriers of filoviruses. These findings offer essential understanding of how the Sudan virus infects cells and its evolutionary background, opening avenues for possible treatments.
Published in Communications Biology, the study was directed by Dr. Fang Li, who is the co-director of the Midwest AViDD Center and a professor of Pharmacology. The research team included graduate student Fan Bu, research scientist Dr. Gang Ye, research assistants Hailey Turner-Hubbard and Morgan Herbst from the Department of Pharmacology, and Dr. Bin Liu from the Hormel Institute. This research was funded by the NIH grant U19AI171954.
