Small Molecule Identified as Key HIV Treatment Target

A multi-institution research team discovers a small molecule that could potentially lead to an effective treatment for HIV.

In 2017, 940,000 people died from Human Immunodeficiency Virus-related (HIV) causes globally. HIV has claimed more than 35 million lives so far, according to the World Health Organization (WHO)

Swaziland has the highest rate of HIV/AIDS infection worldwide, with a total of 27.20 percent of the population affected. In Lesotho, 25.00 percent of the population is infected with HIV/AIDS, making it the second highest rate in the world.

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Botswana has the world's third-largest prevalence rates of HIV/AIDS with 21.90 percent of the population living with the disease. The United States is 24th on the list of the 50 countries with highest rate of HIV/AIDS with a 2.40 percent of its population suffering from the disease, according to Worldatlas

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Human Immunodeficiency virus is a virus that weakens the human immune system, sometimes leading to Acquired Immune Deficiency Syndrome (AIDS). In cases of early detection, HIV can be managed to prevent it from progressing to the final stage of AIDS, which has fatal consequences.

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HIV attacks CD4 cells, exposing the infected person to opportunistic infections. CD4 cells are white blood cells whose isle in paramount to the human immune system, the body's natural defense system against pathogens, infections, and illnesses. CD4 cells are sometimes also called T-cells, T-lymphocytes, or helper cells. 

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Prevention, early diagnosis, treatment, and medical care are essential factors to proper management and control of AIDS which has no cure. HIV is majorly a sexually transmitted disease. However, the virus can be transmitted through blood transfusion and during birth or breastfeeding, as well as through a few other means such as sharing a seringe or piercing.

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Molecule opens door for potential new HIV treatment 

Researchers form Cornell University in collaboration with the University of Delaware (UD), the universities of Virginia and Missouri, the European Molecular Biology Laboratory in Germany and the Institute of Science and Technology in Austria have revealed recent discoveries about the Human Immunodeficiency Virus (HIV) capsid structure and how it develops.

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A capsid is a protein shell that encloses a virus' genetic blueprint. A capsid is made up of 240 proteins.  

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The study conducted by the multi-institutional team focused on the role of a naturally occurring, small molecule called IP6. The study revealed that IP6 plays an important role in both the immature and mature phases of the HIV life cycle as the virus assembles its structure. The research paper Inositol phosphates are assembly co-factors for HIV-1 was published in the journal Nature.

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“This small molecule acts in two different assembly steps in the pathway,” said Robert Dick, a postdoctoral researcher at Cornell University and the first author of the paper. “A cell can make millions of virus particles, but if they don’t go through the maturation process, they are not infectious.”

According to Juan R. Perilla, assistant professor of chemistry and biochemistry at the Uiversity of Delaware, the discovery of the key role played by IP6 opens a door for development of new treatments that would target that molecule.

Research paper co-authors Juan Perilla and doctoral student Chaoyi Xu conducted computational and analytical work using supercomputers from Pittsburgh Supercomputing Center and the Texas Advanced Computing Center to model the capsid of the HIV virus and the role of IP6 in its assembly. 

“Just as we found that HIV uses IP6 to develop and become infectious, we want to learn how retroviruses, in general, learned to use these kinds of molecules,” Perilla said. “Viruses always evolve, but this particular mechanism is especially important." The question that remains unanswered, though, is when the virus evolved. 

“Many experimental techniques are just a snapshot,” Perilla said. However, according to Perilla, using laboratory data in combination with supercomputers it is possible to actually see how things move.

Juan Perilla and Chaoyi Xu ran their simulations using supercomputer resources from the Extreme Science and Engineering Environment (XSEDE) project.

Juan Perilla’s research team has previously done similar types of simulations and analysis on other aspects of HIV and on the hepatitis B virus. In addition to HIV, the researchers have investigated other retroviruses including equine and poultry viruses.

The research was funded by the National Institutes of Health, with supercomputer time allocated by XSEDE. The Texas Advanced Computing Center, at the University of Texas in Austin, designs and operates some of the world's most powerful supercomputing resources.

Via: UDEL

 

 

 

 

 

 

 

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