Scientists at the University of Granada (Spain) lead research that may contribute to the development of new drugs, vaccines and microbicides against HIV-1
Using bright X-rays at the ALBA synchrotron radiation facility near Barcelona, a group of researchers has determined the crystal structure of a synthetic protein chain that can prevent HIV-1 infection
Glycoprotein gp41 is part of the envelope surrounding human immunodeficiency virus (HIV) and is responsible for virus entry into the host cell. During HIV-1 infection, two regions of gp41 (the N-terminal heptad repeat and the C-terminal heptad repeat, NHR and CHR respectively) can temporarily be accessed by inhibitors.
Research led by the University of Granada has designed a single protein chain that mimics the NHR surface and binds with the synthetic CHR peptides. Thus, this chain prevents the virus from infecting the host cell, as previously demonstrated with other pseudovirus and isolated virus. The next step was to grow the protein in crystals and expose these to the high-energy X-rays generated in the ALBA Synchrotron, located on the Autonomous University of Barcelona campus in Cerdanyola del Vallés.
Diffraction X-ray experiments conducted in the XALOC beamline have helped determine the crystal structure of the protein, confirming its ability to perfectly mimic the NHR surface in the gp41 region.
This protein, which is highly stable and precise, has enormous potential in the development of drugs, vaccines and microbicides against HIV-1.
The research was carried out by members of the University of Granada, the University of Almería, PX Therapeutics, Sanofi Pasteur and INSERM, with funding from the European Union’s Euroneut-41 project VII Framework Program and the regional government of Andalusia.
AIDS remains a problem
HIV-1 is the most common pathogenic HIV strain. AIDS remains a global public health problem having claimed the lives of over 39 million people, according to the World Health Organization (WHO). Sub-Saharan Africa is the worst affected region with 24.7 million people living with HIV in 2013 and accounting for 70% of all new HIV infections.
An effective HIV vaccine has yet to be designed. However, effective treatments with antiretroviral drugs that can control the virus do exist. However, these treatments (for example, the drug T20) have some drawbacks: the high doses required, adverse side effects, and high cost. So, new improved compounds are still needed to increase current alternatives in treating and preventing infection by HIV-1.
Figure. Crystallographic structure of the protein chain. Representation of the overlay of the protein within the theoretical model of the gp41 ectodomain.
Reference:
“Single-chainproteinmimetics of the N-terminal heptad-repeatregion of gp41 withpotential as anti-HIV-1 drugs”
Sara Crespillo, Ana Cámara-Artigas, Salvador Casares, Bertrand Morel, Eva S. Cobos, Pedro L. Mateo, Nicolas Mouz, Christophe E. Martin, Marie G. Roger, Raphaelle El Habib, Bin Su, Christiane Moog, Francisco Conejero-Lara.
PNAS 111 (51) 18207–18212, doi: 10.1073/pnas.1413592112
Contact details:
Francisco Conejero-Lara
Department of Physical Chemistry, University of Granada
+34 958 958 242 371
E-mail address: conejero@ugr.es
