Navigation Links
Penn researchers discover new target for preventing and treating flu
Date:1/30/2008

PHILADELPHIA - 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. This study is published in the Jan. 31 issue of the journal Nature.

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.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Researchers investigate links between prostate, cadmium, zinc
2. New nanotube findings by Stanford researchers give boost to potential biomedical applications
3. Researchers Map Paths Governing Neuron Function
4. Cold Spring Harbor Laboratory researchers race against time to save Tasmanian devils
5. Researchers at Peoria Pulmonary Associates to study airway bypass procedure for emphysema
6. Pain medicine meeting unites top researchers and clinicians
7. Researchers identify brains eureka circuitry
8. Researchers find relief for chronic pain
9. Researchers propose consumers buy yearly drug licenses as new way to pay for prescriptions
10. Pros, cons of drug proven to prevent prostate cancer should be considered, researchers recommend
11. DOE awards supercomputing time to UCSD, SDSC researchers
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Penn researchers discover new target for preventing and treating flu
(Date:4/26/2017)... ... , ... Journal of Oral Implantology – Tooth loss is not ... health, including complications with speech, eating, and overcompensation of mouth due to the deficiency. ... As the number of tooth replacements increase, it is imperative to design an implant ...
(Date:4/26/2017)... ... April 26, 2017 , ... Elisabete ... has been honored by Enterprising Women magazine as one of its 2017 Enterprising ... women business owners. Winners have demonstrated that they have fast-growth businesses, mentor or ...
(Date:4/26/2017)... (PRWEB) , ... April 26, 2017 , ... RawTrition now ... easy way to get nutrients from SUPERFOODS! , RawTrition is taking nutrients ... the cellular level because the body recognizes its raw form (unlike the synthetically made ...
(Date:4/26/2017)... ... 26, 2017 , ... MYOLYN, a medical technology company dedicated ... received 510(k) clearance from the U.S. Food & Drug Administration (FDA) for two ... devices are stationary cycling systems that use MYOLYN’s patent-pending functional electrical stimulation ...
(Date:4/25/2017)... ... April 25, 2017 , ... ... to raising awareness for Duchenne muscular dystrophy, and funding for Duchenne research, ... cells) Phase I/II HOPE clinical trial in Duchenne announced today. , Coalition ...
Breaking Medicine News(10 mins):
(Date:4/19/2017)... 19, 2017  Sorrento Therapeutics, Inc. (NASDAQ: ... company developing new treatments for cancer and other ... its previously announced underwritten public offering of 23,625,084 ... offering price of $2.00 per share, before deducting ... payable by Sorrento.  The net proceeds to Sorrento ...
(Date:4/19/2017)... April 19, 2017  Novartis today announced the ... Heart, Lung, and Blood Institute (NHLBI) of the ... of patients with treatment-naïve severe aplastic anemia (SAA) ... with eltrombopag at the initiation of and concurrently ... evaluated three sequential treatment groups, or cohorts. Cohort ...
(Date:4/18/2017)... Cogentix Medical, Inc. (NASDAQ: CGNT), a global medical device ... markets with innovative and proprietary products, will release financial ... after the market close on Tuesday, May 2, 2017. ... call and webcast to discuss its financial results the ... p.m. Eastern Time (3:30 p.m. Central Time). Darin ...
Breaking Medicine Technology: