Researchers from the University of Pennsylvania School of Medicine have found that inhibitors of an enzyme called cathepsin L prevent the SARS (severe acute respiratory syndrome) virus from entering target cells. SARS is caused by an emergent coronavirus. There is no effective treatment at this time. This study also demonstrates a new mechanism for how viral proteins are activated within host cells, states senior author Paul Bates, PhD, an Associate Professor in the Department of Microbiology. Bates and first author Graham Simmons, PhD, Research Associate, also in the Department of Microbiology, published their findings in the early August issue of the Proceedings of the National Academy of Sciences. To gain entry, a virus binds to receptors on the surface of the host cell, and is taken up into a vesicle, or sphere, inside the cell. Unlike most known viruses, the SARS coronavirus (like the Ebola virus) needs one more step to infect the cell. The proteins within the membrane of both SARS and Ebola need to be cut by special cellular enzymes (cathepsins) in order to replicate within the host cell. Cathepsins act in the low pH (acidic) environment inside the vesicle, facilitating fusion of the viral membrane and the vesicle membrane, so that viral proteins and nucleic acids can enter the cell where viral replication occurs.
