HIV, the virus that causes AIDS , has already claimed the lives of more than 35 million people. For this reason, and despite the fact that the progress in its treatment has reduced mortality and has made it almost a chronic disease, finding a definitive cure has been marked with one of the major objectives of modern medicine.
Now, in a study led by the University of Delaware and the School of Medicine at the University of Pittsburgh, a group of researchers has discovered a ‘brake’ that interferes with the development of HIV in an infectious agent. This mechanism prevents the formation of the capsid, that is, the protein coat that covers the virus.
Seven years of detailed studies on the structure and dynamics of HIV at the beginning and end of its life cycle have been needed . The movements of the virus molecules were measured experimentally and simulated in quadrillionths of a second: much faster than the blinking of an eye or the flutter of the wings of a hummingbird.
How is the structure of this virus?
As the HIV virus develops , a cascade of events occurs that affect its structure and infectiousness.
“Viruses like HIV and its constituent proteins and nucleic acid molecules are dynamic entities that expand and reduce constantly, their movements are like breathing .” This is explained by the professor of the Department of Chemistry and Biochemistry of the University of Delaware, Tatyana Polenova.
According to Polenova, the molecules in the HIV virus operate in concert, however, each movement of the molecule occurs at different time scales : a difficult scenario to simulate.
Thanks to state-of-the-art biomedical technology, including high-end computer simulations and cryoelectron microscopy, the researchers answered a question that had not been answered for a long time: how does the final step in the maturation of the virus take place? That is, the process by which an immature, non-infectious virus becomes an infectious virus particle.
The team discovered that a key peptide (SP1) has to be in a highly mobile structure to be cut by the virus protease , the enzyme that acts like a blade. In the simulations, the peptide resembles a thin thread.
Once the SP1 peptide is cut, the HIV virus forms its protective capsid and becomes infectious.
So, how does that process stop? The scientists showed that a certain anti-HIV inhibitor, called anti-HIV Bevirima, interacted with the SPI peptide, thus preventing the development of this capsid of the virus and, therefore, preventing it from becoming infectious.
Concentrating on possible pharmacological targets to prevent HIV from becoming infectious by interrupting the maturation of the virus is a constant goal for the team. But, at the moment, there is no treatment to apply such a finding; Until now, it is limited to the laboratory.