Navigation Links
P7 protein resistance mutations identified; represent drug targets for hepatitis C virus
Date:6/28/2011

British researchers have identified specific resistance mutations for two classes of p7 inhibitor, which may explain their lack of effectiveness in clinical trials combined with current standard of care. Study results support the role of p7 inhibitor combinations as potential components of future HCV-specific therapies and are available in the July issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases.

More than 3% of the world population is infected with HCV, which causes severe liver disease. HCV is the leading cause of liver-related mortality and most common cause for liver transplantation in the U.S. Studies have shown that the current treatment of PEGylated interferon alpha (IFN) and ribavirin (Rib) does not adequately achieve a sustained virological response in many HCV patients. This, coupled with the high cost and poor patient compliance, continues to drive demand for new virus-specific therapies.

"The HCV p7 ion channel plays a critical role in infectious virus production, representing an important new therapeutic target," said lead researcher Dr. Stephen Griffin with the Institute of Molecular Medicine at the University of Leeds in the UK. Previously, Dr. Griffin and colleagues determined that p7 acts as a proton channel within HCV infected cells, and that its function could be blocked by small molecule inhibitors, resulting in a blockade of infectious virus production.

In the present study, the team set out to expand on their prior work by predicting inhibitor binding sites using molecular modeling, which were then validated by the identification of resistance mutations. This allowed the researchers to define the mode of action for two prototype p7 inhibitor classesadamantanes (amantadine and rimantadine) and alkylated imino-sugars (IS). This confirmed not only specific, but distinct effects for these inhibitors on the p7 protein. As these drugs are known to be safe in humans, they could rapidly be combined with new direct-acting HCV drugs, while paving the way for the development of novel, more potent compounds.

Dr. Griffin explains, "Our study confirms that single amino acid changes can mediate resistance to p7 inhibitor drugs." The study describes that low fitness cost for the observed mutations suggest that a minimal genetic barrier to their selection exists, which explains the perceived lack of p7 inhibitor efficacy in clinical trials combined with IFN/Rib. "Further investigation into the molecular basis of p7 drug resistance will aid in the design of novel, more effective therapies to combat HCV," concluded Dr. Griffin.


'/>"/>

Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell
Source:Eurekalert

Related medicine news :

1. New and Delicious, Almond Butter Filled, Cookie Bites With 35.7% Protein to Help Manage Weight and Build Muscle
2. Research highlights role of protein pair in obesity regulation
3. Urine protein test might help diagnose kidney damage from lupus, UT Southwestern researchers find
4. Smithfield, United Food and Commercial Workers Union, and Food Networks Paula Deen to Deliver 150,000 Servings of Protein to San Francisco Food Bank
5. Protein Sciences Corporation Announces Profitable and Cash Flow Positive Results for 2009 and Management Realignment
6. Protein Appears Key to Intestinal Balance
7. SIBLING proteins may predict oral cancer
8. Damaged protein identified as early diagnostic biomarker for Alzheimers disease in healthy adults
9. Cells of aggressive leukemia hijack normal protein to grow
10. Omega Protein Comments on California Lawsuit Alleging Fish Oil Contaminants
11. Proteins May Predict Spread of Colon Cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/30/2016)... ... April 30, 2016 , ... ... President and CEO of EMED, today signed a multifaceted agreement which will allow ... the Northern Caribbean University Department of Natural and Applied Sciences, Allied Health and ...
(Date:4/29/2016)... ... 30, 2016 , ... Mercy College is expanding its Graduate Business Programs to ... expanding due to high demand: Master of Business Administration (MBA), Master of Organizational Leadership ... , School of Business Graduate Program Chair Dr. Ray Manganelli said: “We believe ...
(Date:4/29/2016)... ... 29, 2016 , ... Our bodies are bombarded daily by environmental and lifestyle ... these stressors is to adopt a more healthful diet, but too many people think ... certified Holistic Nutritionist and the creator of the Newport Beach Cleanse and 14-Day Eating ...
(Date:4/29/2016)... ... April 29, 2016 , ... Conditions were ideal for Global Lyme Alliance’s (GLA) ... with sunny skies, a light breeze and temperatures in the 60s. Over 400 runners, ... Run and Walk and 1-mile walk were held to increase awareness about Lyme ...
(Date:4/29/2016)... , ... April 29, 2016 , ... Mobility Designed ... put pressure on the armpits, the M+D Crutch evenly distributes body weight from the ... wrists and hands when using the crutches than with other crutches. , Co-founders Max ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... New market research titled ... report that provides an overview of the Osteoarthritis,s ... identifying new targets and MOAs to produce first-in-class ... in this H1 2016 Osteoarthritis Pipeline report include ... Abiogen Pharma S.p.A., Ablynx NV, Achelios Therapeutics, Inc., ...
(Date:4/27/2016)... 27, 2016 ... in Zürich gab Strekin AG den Start ... zur Erhaltung des Resthörvermögens von Patienten, denen ... die umfassende Phase-II-Doppelblindstudie mit Placebo-Kontrollgruppe werden momentan ... wird während der Operation direkt ins Mittelohr ...
(Date:4/27/2016)... , April 27, 2016   ... 42% Growth in Recurring Consumable Sales  Clinical ... Mauna Kea Technologies (Euronext: MKEA, OTCQX: MKEAY) inventor of ... its sales for the first quarter ended March 31, ... the execution of its commercial strategy. First ...
Breaking Medicine Technology: