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Drug aimed at 2 bioterror agents blocks live viral infection, Weill Cornell team reports
Date:12/19/2007

ctious Diseases' Biodefense Research Agenda have included both viruses as potential bioterror agents.

"Theoretically, it's possible to go out into the field and collect Hendra virus from bats, for example," Dr. Moscona says. "We've been urgently working on this because right now there's absolutely nothing that can be done to stop this fatal, transmissible illness."

Luckily, prior research at Weill Cornell had laid out some important groundwork. The study's lead author, Dr. Matteo Porotto, has worked for years studying these types of microorganisms, using the parainfluenza virus as his model.

"We were able to develop the strategy that we describe in this paper because our work on parainfluenza had already helped us understand how these viruses fuse with host cells," says Dr. Porotto, assistant professor of microbiology in the Department of Pediatrics at Weill Cornell Medical College.

Based on that work, Drs. Porotto and Moscona knew that when the receptor-binding molecule on the virus -- simply called "G" -- binds to the surface of the cell, it activates a special "fusion protein." This fusion molecule has to then undergo some shape changes to turn itself into a six-helix bundle. Once that's done, it helps the virus fuse with, and enter, the cell, Dr. Porotto explains.

However, the Weill Cornell team discovered that a peptide specific to the parainfluenza virus "fusion protein" ("F") can inhibit this shape-changing step -- stopping fusion cold.

"Surprisingly, this parainfluenza F-peptide turned out to be even more effective at inhibiting Hendra virus fusion than peptides derived from the Hendra virus itself," Dr. Moscona says. "It also appears to do much the same thing with the Nipah virus, inhibiting fusion there, too."

The team discovered just why the F peptide works so well in a collaboration with Dr. Min Lu, associate professor of biochemistry at Weill Cornell. "These peptides act like door jambs --
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Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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