Navigation Links
Pitt team finds 'Achilles Heel' of key HIV replication protein
Date:1/24/2013

PITTSBURGH, Jan. 24, 2013 Researchers at the University of Pittsburgh School of Medicine may have found an "Achilles heel" in a key HIV protein. In findings published online today in Chemistry and Biology, they showed that targeting this vulnerable spot could stop the virus from replicating, potentially thwarting HIV infection from progressing to full-blown AIDS.

Previous research demonstrated that a small HIV protein called Nef interacts with many other proteins in infected cells to help the virus multiply and hide from the immune system. The Pitt group developed a way to track Nef activity in high-throughput drug screening protocols by linking it to an enzyme called Hck, which is activated by Nef in HIV-infected cells, explained senior author Thomas E. Smithgall, Ph.D., William S. McEllroy Professor and Chair, Department of Microbiology and Molecular Genetics.

"We reasoned that agents that prevent Nef from its usual interactions with other proteins might be able to stop HIV from replicating and infecting other cells," Dr. Smithgall said. "For this study, we devised an automated screening procedure and tested nearly 250,000 compounds to find ones that could block Nef activity."

One of the compounds they discovered, called B9, seemed particularly potent at blocking Nef. In follow-up experiments, the research team examined how B9 accomplished this and found that it could prevent two Nef molecules from interacting to form dimers as effectively as a mutation in a critical area of the protein surface. The inability of Nef to dimerize consequently impairs its function in the viral replication process.

"This pocket where B9 binds to Nef and where Nef forms a dimer indicates it's a hot spot, or Achilles heel, that could represent a new target for HIV drugs," Dr. Smithgall said. "Our test tube and cell culture experiments show that blocking this site brings HIV replication to a halt."

The team is working with medicinal chemists at the University of Pittsburgh Drug Discovery Institute (DDI) to find analogs of B9 that have therapeutic potential, and plan to assess them in animal models of HIV/AIDS.


'/>"/>
Contact: Anita Srikameswaran
SrikamAV@upmc.edu
412-578-9193
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

Related biology news :

1. Plants adapt to drought but limits are looming, study finds
2. Study finds linchpin of skin response to UVA light
3. Privacy a problem for mothers of newborns in neonatal intensive care units, CWRU study finds
4. Study finds a new culprit for epileptic seizures
5. Born to lead? Leadership can be an inherited trait, study finds
6. Team finds gene that promotes drug resistance in cancer
7. Study finds Jurassic ecosystems were similar to modern: Animals flourish among lush plants
8. Major cuts to surging CO2 emissions are needed now, not down the road, study finds
9. Bering Sea study finds prey density more important to predators than biomass
10. Hebrew University study finds key mechanism in calcium regulation
11. Black piranha, megapiranha have most powerful bites of fish living or extinct, finds GW researcher
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/2/2016)... , June 2, 2016 The Department ... has awarded the 44 million US Dollar project, for the ... Vehicle Plates including Personalization, Enrolment, and IT Infrastructure , ... in the production and implementation of Identity Management Solutions. Numerous ... however Decatur was selected for the ...
(Date:5/20/2016)... MINNEAPOLIS , May 20, 2016  VoiceIt ... technology partnership with VoicePass. By working ... user experience.  Because VoiceIt and VoicePass take slightly ... two engines increases both security and usability. ... expressed excitement about this new partnership. ...
(Date:4/28/2016)... SAN FRANCISCO and BANGALORE, India ... part of EdgeVerve Systems, a product subsidiary of Infosys (NYSE: ... service provider, today announced a global partnership that ... convenient way to use mobile banking and payment services. ... Mobility is a key innovation area for financial services, but ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... ... Researchers at the Universita Politecnica delle Marche in Ancona combed medical journal articles ... findings are the subject of a new article on the Surviving Mesothelioma website. ... blood, lung fluid or tissue of mesothelioma patients that can help point doctors to ...
(Date:6/23/2016)... , June 23, 2016   Boston Biomedical ... novel compounds designed to target cancer stemness pathways, ... been granted Orphan Drug Designation from the U.S. ... of gastric cancer, including gastroesophageal junction (GEJ) cancer. ... designed to inhibit cancer stemness pathways by targeting ...
(Date:6/23/2016)... , June 23, 2016 Houston Methodist ... the Cy-Fair Sports Association to serve as their ... agreement, Houston Methodist Willowbrook will provide sponsorship support, ... connectivity with association coaches, volunteers, athletes and families. ... the Cy-Fair Sports Association and to bring Houston ...
(Date:6/23/2016)... NEW YORK , June, 23, 2016  The ... students to envision new ways to harness living systems ... of Modern Art (MoMA) in New York ... more than 130 participating students, showcased projects at MoMA,s ... included Paola Antonelli , MoMA,s senior curator of ...
Breaking Biology Technology: