Featured Research

from universities, journals, and other organizations

New Target For Preventing And Treating Flu Discovered

Date:
February 6, 2008
Source:
University of Pennsylvania School of Medicine
Summary:
Researchers have now provided a new strategy for designing drugs that target resistant viral strains of inflenza tupe A by solving the three-dimensional structure of a viral protein called the M2 proton channel. This protein is the molecular receptor for these drugs.

Structure of amantadine inside viral binding site.
Credit: William F. DeGrado, PhD, University of Pennsylvania School of Medicine

Emerging subtypes of influenza A virus hold the potential to initiate a world-wide epidemic in the next few years, according to World Health Organization officials. However, almost all type A influenza viral strains have become resistant to amantadine and rimantadine, two drugs that make up one of only two classes used to treat the flu.

Researchers at the University of Pennsylvania School of Medicine have now provided a new strategy for designing drugs that target the resistant viral strains by solving the three-dimensional structure of a viral protein called the M2 proton channel. This protein is the molecular receptor for these drugs.

The M2 protein is located in the viral envelope, forming a long, narrow channel that allows the flow of protons into the viral interior, an essential step for infection. Amantadine sits in this channel and blocks the flow of protons, thus halting infection. In non-resistant viruses, amantadine acts like a cork lodged deep in the channel.

"We know that resistance to amantadine is caused by a mutation in the virus M2 protein, but we did not know how this mutation caused resistance," explains senior author William F. DeGrado, PhD, Professor of Biochemistry and Biophysics. "Now we do -- the mutation changes the shape of the channel so amantadine can no longer do its job."

The structure revealed that there is a pocket in the channel next to the location where amantadine fits that is conserved in all influenza A viruses. This newly discovered space could be the target for new drugs. "Inhibitors that target this cavity adjacent to two highly conserved amino acids in M2 might reclaim the M2-blocking class of drugs so that ongoing endemic outbreaks and future pandemics of this deadly virus might be prevented and treated," says DeGrado.

"The crystal structures of influenza M2 with and without the anti-influenza drug help us understand the molecular basis of drug resistance, which is a serious problem in treating the flu," said Jean Chin, PhD, who oversees grants on membrane proteins at the National Institute of General Medical Sciences, which in part funded this research. "The findings will inform scientists working to design the next generation of antivirals."

The M2 protein was crystallized so that its structure could be examined under different conditions. This allowed the Penn research team, which included Amanda Stouffer, Rudresh Acharya, David Salom, Cinque Soto, Luigi Di Costanzo, Steven Stayrook, Vikas Nanda, and Anna Levine, to determine the structure of the crystallized protein using a technique called x-ray crystallography.

The pure protein crystal was bombarded with x-rays so that the position of each atom in relation to its neighboring atoms in the crystal would show up as an array of black spots. From the pattern of thousands of spots, the structure of the protein can be graphically visualized using computer imaging technology.

The next step is to design new compounds that plug the M2 channel by fitting into the newly discovered larger cavity. The Penn research group is currently engaged in these studies.

This study is published in the Jan. 31 issue of the journal Nature. Valentina Tereshko of the University of Chicago also contributed to this study.

This study was supported by the National Institute of General Medical Studies, the Kimberly and Margaret DeLape Fellowship, the University of Pennsylvania's MRSEC program, and the National Science Foundation.


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University of Pennsylvania School of Medicine. "New Target For Preventing And Treating Flu Discovered." ScienceDaily. ScienceDaily, 6 February 2008. <www.sciencedaily.com/releases/2008/01/080130161753.htm>.
University of Pennsylvania School of Medicine. (2008, February 6). New Target For Preventing And Treating Flu Discovered. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2008/01/080130161753.htm
University of Pennsylvania School of Medicine. "New Target For Preventing And Treating Flu Discovered." ScienceDaily. www.sciencedaily.com/releases/2008/01/080130161753.htm (accessed October 21, 2014).

Share This



More Plants & Animals News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

White Lion Cubs Born in Belgrade Zoo

White Lion Cubs Born in Belgrade Zoo

AFP (Oct. 20, 2014) Two white lion cubs, an extremely rare subspecies of the African lion, were recently born at Belgrade Zoo. They are being bottle fed by zoo keepers after they were rejected by their mother after birth. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Traditional Farming Methods Gaining Ground in Mali

Traditional Farming Methods Gaining Ground in Mali

AFP (Oct. 20, 2014) He is leading a one man agricultural revolution in Mali - Oumar Diatabe uses traditional farming methods to get the most out of his land and is teaching others across the country how to do the same. Duration: 01:44 Video provided by AFP
Powered by NewsLook.com
Goliath Spider Will Give You Nightmares

Goliath Spider Will Give You Nightmares

Buzz60 (Oct. 20, 2014) An entomologist stumbled upon a South American Goliath Birdeater. With a name like that, you know it's a terrifying creepy crawler. Sean Dowling (@SeanDowlingTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Adorable Video of Baby Rhino and Lamb Friend Playing

Adorable Video of Baby Rhino and Lamb Friend Playing

Buzz60 (Oct. 20, 2014) Gertjie the Rhino and Lammie the Lamb are teaching the world about animal conservation and friendship. TC Newman (@PurpleTCNewman) has the adorable video! Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins