http://www.sciencecodex.com/speeding_up_drug_...mapping_of_proteins-92363

Speeding up drug discovery with rapid 3-D mapping of proteins
Posted On: May 30, 2012 - 1:30pm

LA JOLLA, CA----A new method for rapidly solving the three-dimensional structures of a special group of proteins, known as integral membrane proteins, may speed drug discovery by providing scientists with precise targets for new therapies, according to a paper published May 20 in Nature Methods. The technique, developed by scientists at the Salk Institute for Biological Studies, provides a shortcut for determining the structure of human integral membrane proteins (hIMPs), molecules found on the surface of cells that serve as the targets for about half of all current drugs. Knowing the exact three-dimensional shape of hIMPs allows drug developers to understand the precise biochemical mechanisms by which current drugs work and to develop new drugs that target the proteins. "Our cells contain around 8,000 of these proteins, but structural biologists have known the three-dimensional structure of only 30 hIMPs reported by the entire field over many years," [...] "We solved six more in a matter of months using this new technique. The very limited information on the shape of human membrane proteins hampers structure-driven drug design, but our method should help address this by dramatically increasing the library of known hIMP structures." Integral membrane proteins are attached to the membrane surrounding each cell, serving as gateways for absorbing nutrients, hormones and drugs, removing waste products, and allowing cells to communicate with their environment. Many diseases, including Alzheimer's, heart disease and cancer have been linked to malfunctioning hIMPs, and many drugs, ranging from aspirin to schizophrenia medications, target these proteins. Most of the existing drugs were discovered through brute force methods that required screening thousands of potential molecules in laboratory studies to determine if they had a therapeutic effect. Given a blueprint of the 3D structure of a hIMP involved in a specific disease, however, drug developers could focus only on molecules that are most likely to interact with the target hIMP, saving time and expense. [...] using their new method, the Salk scientists determined the structure of six hIMPs within just 18 months. They have already identified 38 more hIMPs that are suitable for analysis with their technique, and expect it will be used to solve the structure for many more.

http://www.infectioncontroltoday.com/news/201...ell-receptor-protein.aspx

[...] Several studies have found that particular versions of a molecule called HLA-B, which helps to flag infected cells for destruction by CD8 T cells, are associated with the ability to naturally control HIV infection. But even among individuals who inherit those versions or alleles of HLA-B, only a few are HIV controllers. A 2010 Ragon Institute study published in Science identified five amino acids within HLA-B that appear to affect the ability to control infection, but that study only explained about 20 percent of the difference in viral load between controllers and individuals in whom the infection progressed. The current study was designed to search for other factors besides HLA-B that contribute to and possibly determine the ability to control HIV infection. [...] The experiments first confirmed there was no significant difference in the number of HIV-specific CD8 T cells between controllers and progressors but also found significant variability in the protein sequence of all participants' T cell receptors. Tests of particular functional aspects of the CD8 T cell response found that a subset of cells from controllers were quite efficient at killing infected cells and able to respond to HIV mutations that can allow the virus to escape immune control. No such effective cells were found in samples from progressors. Detailed sequencing of HIV-specific CD8 cells from three controllers and two progressors found that the specific protein sequence of T cell receptors – which affects their structure and ability to recognize infected cells – appears to make the difference. [...]

http://www.sciencedaily.com/releases/2012/06/120614182751.htm

ScienceDaily (June 14, 2012) — More than 15 percent of new HIV infections occur in children. Without treatment, only 65 percent of HIV-infected children will live until their first birthday, and fewer than half will make it to the age of two. Although breastfeeding is attributed to a significant number of these infections, most breastfed infants are not infected with HIV, despite prolonged and repeated exposure. HIV researchers have been left with a conundrum: does breast milk transmit the virus or protect against it? [Research now shows that human] breast milk has a strong virus killing effect and protects against oral transmission of HIV. [...]

"A crucial new low-cost blood test for HIV sufferers in developing countries that could help 33 million people worldwide may be available later this year.

The simple test developed by researchers at Melbourne's Burnet Institute shows how much damage the HIV virus has done to the immune system and whether lifesaving antiretroviral drugs are required. The finger-prick blood test would ideally target developing African and Asian countries where laboratories and expensive equipment normally needed to carry out the tests are scarce, said Co-head of Burnet's Centre for Virology Professor Suzanne Crowe.

The CD4 test, which gives on-the-spot results in 40 minutes, measures an individual's CD4 levels, which indicate whether HIV is progressing to AIDS.

"It will tell the health worker if the person's immune system has declined to the level where they require treatment for HIV," said Prof Crowe, who developed the test with Burnet Institute deputy director Associate Professor David Anderson.

Prof Anderson said the device could provide cost-effective testing for up to 33 million patients worldwide. Another CD4 test is currently available for developing countries but it is more expensive, requires medical equipment and trained health workers to extract blood from veins.

The new test will cost less than $2, which would probably be subsidised by governments or philanthropic organisations, and works a bit like a pregnancy test in terms of its immediacy, Prof Crowe said."

http://news.ninemsn.com.au/health/8486871/low...an-hiv-test-to-reach-poor

http://www.bio-medicine.org/biology-news-1/Ne...y-news+%28Biology+News%29

"6/13/2012

New drug-screening method yields long-sought anti-HIV compounds

LA JOLLA, CA June 13, 2012 Scientists at The Scripps Research Institute have used a powerful new chemical-screening method to find compounds that inhibit the activity of human immunodeficiency virus (HIV), the virus that causes AIDS. Unlike existing anti-HIV drugs, the compounds bind to a protein called "nucelocapsid," which is unlikely to mutate into drug-resistant forms.

"Most of the nucleocapsid-inhibiting compounds that have been identified to date are very toxic, but our screening method identified inhibitors that are less toxic and thus more likely to lead to useful drugs," said Scripps Research Associate Professor Bruce Torbett. Torbett is the senior author of the new report, which appears in the June 14, 2012 print issue of the Journal of Medicinal Chemistry.

HIV's nucleocapsid protein binds to the viral genome to package and protect it, and plays a key role in the assembly of new virus copies, as well as in the reverse transcription of the viral genome into DNA. It has long been a target of HIV drug developers because it grabs hold of the viral genome using protein structuresknown as zinc knucklesthat can't change much without losing their functionality. It thus is thought to have little room to mutate into drug-resistant forms, in contrast with other HIV proteins..."