Featured Research

from universities, journals, and other organizations

Chemists discover how antiviral drugs bind to and block flu virus

Date:
February 4, 2010
Source:
Iowa State University
Summary:
Researchers have determined where an antiviral drug binds to and blocks a channel necessary for the flu virus to spread. The team also discovered that the drug spins in the channel, meaning there could be room for developing drugs that do a better job blocking the channel and stopping the flu.

Chemists from Iowa State University and the Ames Laboratory, left to right, Sarah Cady (who's holding a nuclear magnetic resonance probe), Mei Hong and Klaus Schmidt-Rohr are studying antiviral drugs and how they bind to flu viruses.
Credit: Bob Elbert/Iowa State University

Antiviral drugs block influenza A viruses from reproducing and spreading by attaching to a site within a proton channel necessary for the virus to infect healthy cells, according to a research project led by Iowa State University's Mei Hong and published in the Feb. 4 issue of the journal Nature.

Hong, Iowa State's John D. Corbett Professor of Chemistry and an associate scientist for the U.S. Department of Energy's Ames Laboratory, said the findings clarify previous, conflicting studies and should pave the way to development of new antiviral drugs against influenza viruses, including pandemic H1N1.

Two papers published by Nature in 2008 came to different conclusions about where the antiviral drug amantadine binds to a flu virus and stops it from infecting a healthy cell. A paper based on X-ray studies concluded the drug attached to the lumen of the proton channel, the area inside the channel, and stopped the virus by blocking the channel. Another paper based on solution nuclear magnetic resonance (NMR) technology concluded the drug attached to the surface of the virus protein near the proton channel and stopped the virus by indirectly changing the channel structure.

Hong's research concluded that when amantadine is present at the pharmacologically relevant amount of one molecule per channel, it attaches to the lumen inside the proton channel. But the paper also reports that when there are high concentrations of amantadine in the membrane, the drug will also attach to a second site on the surface of the virus protein near the channel.

"Our study using solid-state NMR technology unequivocally shows that the true binding site is in the channel lumen, while the surface-binding site is occupied only by excess drug," Hong said. "The previous solution NMR study used 200-fold excess drug, which explains their observation of the surface-binding site. The resolution of this controversy means that medical chemists can now try to design new drugs to target the true binding site of the channel."

Here's how a flu virus uses its proton channel and how amantadine blocks that channel:

The virus begins an infection by attaching itself to a healthy cell. The healthy cell surrounds the flu virus and takes it inside the cell through a process called endocytosis. Once inside the cell, the virus uses a protein called M2 to open a channel to the healthy cell. Protons from the healthy cell flow through the channel into the virus and raise its acidity. That triggers the release of the virus' genetic material into the healthy cell. The virus hijacks the healthy cell's resources and uses them to reproduce and spread.

When amantadine binds to and blocks the M2 proton channel, the process doesn't work and a virus can't infect a cell and spread.

Hong and the research team developed powerful techniques to study the proton channel using solid-state NMR spectroscopy, the technology behind medical magnetic resonance imaging. The techniques provided the researchers with a detailed look at the antiviral drug within the proton channel, showed them the structure of the protein at the drug-binding site and allowed them to make accurate measurements of the distances between the drug and the protein.

The researchers also found that amantadine spins when it binds to the inside of the proton channel. That means it doesn't fill the channel. And Hong said that leaves room for development of other drugs that do a better job blocking the channel, stopping the flu and evading development of drug resistance.

Other contributors to the study are Klaus Schmidt-Rohr, an Iowa State professor of chemistry and a senior chemist for the Ames Laboratory; Sarah Cady, a postdoctoral research associate in Iowa State's chemistry department; William DeGrado, the George W. Raiziss Professor of Biochemistry and Biophysics and adjunct professor of chemistry at the University of Pennsylvania; Cinque S. Soto, a postdoctoral researcher in the University of Pennsylvania's department of biochemistry and biophysics; and Jun Wang, a graduate student in the University of Pennsylvania's department of chemistry.

The research project was supported by grants of $687,411 from the National Science Foundation and $616,295 from the National Institutes of Health.


Story Source:

The above story is based on materials provided by Iowa State University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sarah D. Cady, Klaus Schmidt-Rohr, Jun Wang, Cinque S. Soto, William F. DeGrado & Mei Hong. Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers. Nature, 2010; 463 (7281): 689 DOI: 10.1038/nature08722

Cite This Page:

Iowa State University. "Chemists discover how antiviral drugs bind to and block flu virus." ScienceDaily. ScienceDaily, 4 February 2010. <www.sciencedaily.com/releases/2010/02/100203131407.htm>.
Iowa State University. (2010, February 4). Chemists discover how antiviral drugs bind to and block flu virus. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2010/02/100203131407.htm
Iowa State University. "Chemists discover how antiviral drugs bind to and block flu virus." ScienceDaily. www.sciencedaily.com/releases/2010/02/100203131407.htm (accessed April 18, 2014).

Share This



More Plants & Animals News

Friday, April 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Vermont Goat Meat Gives Refugees Taste of Home

Vermont Goat Meat Gives Refugees Taste of Home

AP (Apr. 18, 2014) Dairy farmers and ethnic groups in Vermont are both benefiting from a unique collaborative effort that's feeding a growing need for fresh and affordable goat meat. (April 18) Video provided by AP
Powered by NewsLook.com
First Ever 'Female Penis' Discovered In Animal Kingdom

First Ever 'Female Penis' Discovered In Animal Kingdom

Newsy (Apr. 18, 2014) Not only are these newly discovered bugs' sex organs reversed, but they also mate for up to 70 hours. Video provided by Newsy
Powered by NewsLook.com
The Great British Farmland Boom

The Great British Farmland Boom

Reuters - Business Video Online (Apr. 17, 2014) Britain's troubled Co-operative Group is preparing to cash in on nearly 18,000 acres of farmland in one of the biggest UK land sales in decades. As Ivor Bennett reports, the market timing couldn't be better, with farmland prices soaring over 270 percent in the last 10 years. Video provided by Reuters
Powered by NewsLook.com
Flamingo Frenzy Ahead of Zoo Construction

Flamingo Frenzy Ahead of Zoo Construction

AP (Apr. 17, 2014) With plenty of honking, flapping, and fluttering, more than three dozen Caribbean flamingos at Zoo Miami were rounded up today as the iconic exhibit was closed for renovations. (April 17) Video provided by AP
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:
from the past week

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