Release date: 2017-12-04
Researchers from the University of Delaware and the University of Pittsburgh have discovered a special "brake" mechanism that can effectively interfere with the conversion of HIV into an infectious agent, a mechanism that effectively inhibits viral surface capsid proteins. The formation of the first study was published in the international journal Nature Communications; the results of this study are based on the researchers' detailed study of HIV structure and dynamics in the early and late stages of life cycle. The researchers can detect the molecular trajectories of the virus through experimental methods.
Professor Tatyana Polenova said that researchers are often accustomed to studying the fixed structure of the virus, but the virus is not as static as rocks. In this study, we used nuclear magnetic resonance (NMR) spectroscopy to identify each of the HIV structures. The location of the atoms and how they move. Viruses such as HIV and their constituent proteins, nucleic acid molecules are essentially in the process of dynamic changes, which will continue to expand and contract, and these movements are like breathing.
As HIV begins to develop, a series of cascade events can occur that affect the structure and infection of the virus, by integrating solid and liquid NMR techniques, high-end computer simulation techniques, and low-temperature electron microscopy techniques. The researchers deeply analyzed the final steps of HIV virus maturation, in which non-infectious immature virions were transformed into infectious virus particles.
The researchers found that a peptide molecule called SP1 (spacer peptide 1, spacer peptide 1) exists in a highly motility structure and is cleaved by viral proteases; Peptides are similar to a fine line adsorbed on a fixed spiral ribbon, which always exists in the final stage of viral maturation. Once SP1 is cut, HIV forms a protective capsid and is infectious. So how to effectively block the process? The researchers said that by infecting SP1 peptide molecules, it can effectively inhibit the production of HIV protective capsids.
The researchers then focused their attention on developing potential drugs to effectively block the production of infectious HIV by infecting the virus. Researcher Perilla said that we must understand these short-term molecular fluctuations, the process of the production of the peptide cutter virus capsid, in order to add a capsid inhibitor to block the maturation of HIV, we must constantly study to explore how The use of drugs can effectively block the production of viral capsids, thereby inhibiting the production of infectious HIV.
In later studies, researchers will also develop new drugs to suppress the production of infectious HIV based on the results of this study, and provide new treatments for the effective treatment of HIV patients.
Original source:
Wang M, Quinn CM, Perilla JR, et al. Quenching protein dynamics interferes with HIV capsid maturation. Nat Commun. 2017 Nov 24;8(1):1779. doi: 10.1038/s41467-017-01856-y
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