Researchers at the University of Heidelberg have demonstrated that a particular substance is able to prevent the assembly of the viral envelope – at least in a test tube. The peptide that is known as a “capsid assembly inhibitor” (CAI) binds to a specific structure of the Gag protein, in which prevents the formation of immature and mature viral particles.
Researchers at the University of Heidelberg have discovered a new starting point for developing new anti-HIV medication. They succeeded in preventing the assembly of the viral protein envelope in the laboratory using a particular peptide. They were also able to identify the particular target site of the peptide. This most promising research, undertaken by a group of researchers led by Professor Dr. Hans-Georg Kräusslich, Director of the Department of Virology at the University Hospital in Heidelberg, has just been published in the online edition of the well-known journal “Nature Structural and Molecular Biology”.
An estimated 40 million people are infected worldwide with HIV. Last year, the estimated number increased by some 5 million people and 3 million people died from the effects of AIDS. The numbers are continually increasing. New drugs are desperately needed. HIV infection cannot be cured and the virus has been mutating in order to resist current drugs.
The assembly of viruses as a new target for alternative medicine
The attack of viruses and their propagation in the human body goes through different phases during which the viruses use different tools. These tools are potential targets in the development of effective antiviral drugs.
The researchers in Heidelberg have investigated a particular step in the propagation cycle of HIV, namely the assembly of new viruses in infected cells. The intruding viruses start to propagate in the host cell and immature viral particles leave the cell. These particles have a protein envelope consisting of Gag proteins. Outside the host cell, the viruses dissolve this protein envelope and complex restructuring processes lead to the mature and infectious viral structure, which is now characterised by an altered protein envelope (capsid) containing the genetic information and important viral proteins.
"We were able to prevent the assembly of an immature Gag envelope and the capsid in a test tube with a new substance,” said Professor Kräusslich summarising their results. The peptide that is known as a “capsid assembly inhibitor” (CAI) binds to a specific structure of the Gag protein, in which prevents the formation of immature and mature viral particles.
Structural analyses demonstrate how the peptide docks to the viral envelope
The researchers and their research partners had another success story in that they were able to provide new insights into the molecular structure of HIV particles. X-ray examinations revealed the three-dimensional structure of the complex comprising CAI peptide and Gag protein, which is the target of the peptide.
Unfortunately, the researchers cannot use CAI as medicine as the cells cannot absorb the substance. “However, our experimental results have discovered a new vulnerability in HIV that forms the basis for the targeted search for potential substances affecting the assembly of the virus and to develop new anti-HIV medicines,” said Professor Kräusslich underlining the importance of their work.
Source: University of Heidelberg, 26.07.05
Contact:
Prof. Dr. Hans-Georg Kräusslich
Phone: +49 (0)6221 / 56 50 02 (Secretarial Office)
E-mail:
hans-georg.kraeusslich@med.uni-heidelberg.de
References:
1. A peptide inhibitor of HIV-1 assembly in vitro. Jana Sticht, Michael Humbert, Stuart Findlow, Jochen Bodem, Barbara Müller, Ursula Dietrich, Jörn Werner & Hans-Georg Kräusslich. Published online: 24 July 2005 | doi:10.1038/nsmb964
2. The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitor. François Ternois, Jana Sticht, Stéphane Duquerroy, Hans-Georg Kräusslich & Félix A Rey. Published online: 24 July 2005 | doi:10.1038/nsmb967
(Die Originalartikel könnnen bei der Pressestelle des Universitätsklinikums Heidelberg unter
contact@med.uni-heidelberg.de angefordert werden)
Further information:
Dr. Annette Tuffs
Press and Public Relations Office
of the University Hospital Heidelberg and the
Medical Faculty of the University of Heidelberg
Im Neuenheimer Feld 672
69120 Heidelberg
Phone: +49 (0)6221 / 56 45 36
Fax: +49 (0)6221 / 56 45 44
Mobile: +49 (0)170 / 57 24 725
E-mail:
Annette_Tuffs@med.uni-heidelberg.de
source:
http://www.bio-pro.de/en/region/rhein/magazin/01497/ 
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