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

NEW YORK (Dec. 19, 2007) -- Two deadly and highly infectious viruses -- both potential bioterror threats -- may have met their match in a new drug developed by scientists at Weill Cornell Medical College in New York City.

Hendra and Nipah viruses are related, newly recognized zoonotic viruses that can spread from their natural reservoir in fruit bats to larger animals -- including pigs, horses and humans.

The mode of transmission isn't clear, but is thought to be relatively easy -- either by close contact with an infected host or by breathing in the microscopic pathogens. Infection often leads to a fatal encephalitis, and there is currently no effective treatment against these illnesses.

However, in breakthrough research conducted last year, researchers at Weill Cornell manipulated a peptide (protein) related to a third pathogen, parainfluenza virus, that appeared to block "pseudo" Hendra and Nipah viruses from entering and infecting human cells.

Now, this "entry inhibitor" approach has proven effective in blocking the infection of live virus in animal cells, pointing the way to a drug that could be stockpiled to help stop an outbreak in humans.

Those findings appeared recently in the Journal of Virology.

"We have now tested the peptide-based entry inhibitor in monkey cells to show that it does effectively block infection with both live Hendra and Nipah," explains study senior researcher Dr. Anne Moscona, a professor of pediatrics and of microbiology and immunology at Weill Cornell Medical College, and an attending physician at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

Public health officials have sounded alarm bells ever since Nipah virus first emerged in pigs and then humans living in Southeast Asia. More recently, cases of Hendra virus began to show up in horses and their human handlers in Australia.

Experts who drew up the U.S. National Institute of Allergy and Infectious 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 -- their particular shapes prevent 'doors' in the viral 'fusion protein' from closing as they should. The parainfluenza peptide's shape simply makes it a better door jamb," Dr. Porotto said.

Much of this research is modeled on insights gained from two decades of investigation into another lethal virus, HIV. In fact, T-20, or Fuzeon -- one of the earliest effective HIV-suppressing drugs -- acts on a similar principle to block that virus' entry into cells.

The next step, according to the researchers, is to use what they've learned to design even more effective peptides that should work even better.

"However, one issue with peptides is that you have to be concerned about how long they are going to last in the bloodstream," Dr. Moscona says. "So, we are also developing methods of sustained-release -- for example, encasing the peptide in a polymer pellet that would be injected under the skin. The pellet would then release the drug slowly over the course of a week. That could form a viable method suitable for stockpiling," she says.


'/>"/>

Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

Related biology news :

1. Using evolution, UW team creates a template for many new therapeutic agents
2. Primate behavior explained by computer agents
3. Building blocks of life
4. Natural product discovery by Cleveland medical researchers blocks tissue destruction
5. Scripps research team blocks bacterial communication system to prevent deadly staph infections
6. Building blocks of life formed on Mars
7. Clearance of hepatitis C viral infection after liver transplantation
8. Feline virus, antiviral drug studied to understand drug resistance
9. Cornell will host the Northeast Biofuel Summit, Nov. 11-13
10. First symposium of UN University-Cornell Africa Series to be held at UN
11. Wiggle room: Cornell researcher borrows idea from sperm to provide energy for nanoscale robots
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/16/2016)... Research and Markets has announced the addition of the ... report to their offering. ... The biometric vehicle access system market, in terms of ... 2016 to 2021. The market is estimated to be USD 442.7 ... 2021. The growth of the biometric vehicle access system market is ...
(Date:12/15/2016)... Canada and BADEN-BADEN, Germany , ... a leading global financial services provider, today announced an agreement ... passive behavioural biometrics, to join forces. The partnership will enable ... mitigation strategies in compliance with local data protection regulation. ... In order ...
(Date:12/15/2016)... ... Research and Markets has announced the addition of the "Global ... The report forecasts the global military biometrics market to grow at a ... has been prepared based on an in-depth market analysis with inputs from ... over the coming years. The report also includes a discussion of the ...
Breaking Biology News(10 mins):
(Date:1/12/2017)... NE (PRWEB) , ... January 12, 2017 , ... ... hiring of Stephen Beck, who will work in the company’s Lincoln office as a ... chemical processes to design control systems for customers in the life science manufacturing and ...
(Date:1/12/2017)...   Protein Sciences Corporation , a leading ... Influenza Vaccine ®, announced today that its lead ... results and induced strong neutralizing antibodies against the ... expected to advance into human clinical trials in ... of Technology in Immunobiologicals of the Oswaldo Cruz ...
(Date:1/12/2017)... ... January 12, 2017 , ... ... Limfinity® Cloud, RURO has enhanced the platform to accommodate increasingly complex and ... rapid data searching, and more. In addition to these improvements, the latest ...
(Date:1/11/2017)... ... January 11, 2017 , ... As a graduate student, ... the pathogens that cause malaria and tuberculosis. Seeing firsthand the ravages those diseases ... Now, as an assistant professor of biology and biotechnology at Worcester Polytechnic Institute ...
Breaking Biology Technology: