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:6/25/2016)... , ... June 25, 2016 , ... Conventional wisdom preaches ... success. In terms of the latter, setting the bar too high can result in ... than just slow progress toward their goal. , Research from PsychTests.com ...
(Date:6/24/2016)... ... 2016 , ... Marcy was in a crisis. Her son James, eight, was out of control. ... and physically. , “When something upset him, he couldn’t control his emotions,” remembers Marcy. ... rocks at my other children and say he was going to kill them. If ...
(Date:6/24/2016)... ... 24, 2016 , ... Comfort Keepers® of San Diego, CA is excited to ... Recovery® program to drive cancer patients to and from their cancer treatments. Comfort ... quality of life and ongoing independence. Getting to and from medical treatments is ...
(Date:6/24/2016)... ... June 24, 2016 , ... The ... recognize Dr. Barry M. Weintraub as a prominent plastic surgeon and the network’s ... the world, and the most handsome men, look naturally attractive. Plastic surgery should ...
(Date:6/24/2016)... ... June 24, 2016 , ... Venture Construction Group (VCG) ... held on June 20th at the Woodmont Country Club at 1201 Rockville Pike, Rockville, ... dedicated to helping service members that have been wounded in battle and their families. ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... Roche (SIX: RO, ROG; OTCQX: RHHBY) announced ... BRAHMS PCT (procalcitonin) assay as a dedicated testing solution ... this clearance, Roche is the first IVD company in ... sepsis risk assessment and management. PCT is ... levels in blood can aid clinicians in assessing the ...
(Date:6/23/2016)... 23, 2016 Bracket , a leading clinical ... generation clinical outcomes platform, Bracket eCOA (SM) 6.0, at ... 26 – 30, 2016 in Philadelphia , ... Outcome Assessment product of its kind to fully integrate with ... Bracket eCOA 6.0 is a flexible platform for electronic clinical ...
(Date:6/23/2016)... Revolutionary technology includes multi-speaker listening ... industry leaders in advanced audiology and hearing aid technology, ... ™, the world,s first internet connected hearing aid that ...      (Photo: http://photos.prnewswire.com/prnh/20160622/382240 ) , ... ,world firsts,: , TwinLink™ - the first ...
Breaking Medicine Technology: