Rice University researchers have systematically mapped out, atom by atom, the structure of the shell of the hepatitis E virus. Obviously, the knowledge of the morphology of this particularly nasty strain of hepatitis may help us to develop vaccines or therapies against Hep E.
Tao’s [Yizhi Jane Tao, assistant professor of biochemistry and cell biology] lab specializes in X-ray crystallography, a powerful technique that can pinpoint the exact location of every atom in a biomacromolecule or a large biomacromolecular assembly. In this case, the assembly was the viral capsid shell, made from a network of individual capsid proteins from a strain of HEV that had been made in insect cells, then purified and crystallized.
After two years of intense study, Guu [Rice graduate student Tom Guu –ed.] calculated the position of each of the approximately 500,000 atoms that make up the capsid, an icosahedron-shaped particle that roughly resembles a buckyball. The resulting 3-D computer model gives researchers the ability to identify the particle’s host-cell binding sites, through which HEV spreads.
“Dr. Tao has already identified potential sites on the new model,” said Guu. “If we can prove these sites to be correct, labs around the world can start to design drugs, called competitive inhibitors, to interrupt the binding process and prevent the virus from attaching to cell receptors in the first place.”
Guu compared the virus’s capsid protein to a hollowed-out watermelon. “You have the outer shell of the virus, but you take out its insides,” he said. “It retains its outside properties.” The empty capsid may still bind to a cell, but it contains no genetic material to transfer, rendering it noninfectious and therefore an excellent candidate for a vaccine.
Official statement from Rice: Fighting disease atom by atom…
Abstract in PNAS: Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding