Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps Research Scientists Show Potent New Compound Virtually Eliminates HIV in Cell Culture

20.07.2012
A new study by scientists on the Florida campus of The Scripps Research Institute shows, in cell culture, a natural compound can virtually eliminate human immunodeficiency virus (HIV) in infected cells. The compound defines a novel class of HIV anti-viral drugs endowed with the capacity to repress viral replication in acutely and chronically infected cells.

The HIV/AIDS pandemic continues to affect 34 million individuals worldwide, including more than 3 million children, according to the World Health Organization. Current treatment involves the use of several antiretroviral drugs, termed Highly Active Antiretroviral Therapy (HAART), which can extend the life expectancy of HIV-positive individuals and decrease viral load without, however, eradicating the virus.

“We know that there are reservoirs of HIV that aren’t being eliminated by current treatment and that keep replenishing the infection,” said Susana Valente, a Scripps Research biologist who led the study. “Viral production from these cellular reservoirs that harbor an integrated viral genome is not affected by current antiretroviral drugs, which only stop novel rounds of infection. The compound in the current study virtually eliminates all viral replication from already-infected cells where HIV hides.”

The new study, published in the July 20, 2012 issue of the journal Cell Host and Microbe, focused on a medically promising compound known as Cortistatin A. This natural product was isolated in 2006 from a marine sponge, Corticium simplex, discovered more than 100 years ago. In 2008, Scripps Research chemist Phil Baran and his team won the global race to synthesize the compound, presenting an efficient and economical method.

In the new study, Valente and her colleagues collaborated with the Baran lab, using a synthetic version of the compound, didehydro-Cortistatin A, to study the compound’s effect on two strains of HIV. The strains were HIV-1, the most common form of the virus, and HIV-2, which is concentrated in West Africa and some parts of Europe.

The results showed that the compound reduced viral production by 99.7 percent from primary CD4+T cells (a type of immune cell) isolated from patients without levels of the virus in their bloodstream and who had been under HAART treatment for a long period of time. When the compound was added to other antiviral treatments, it further reduced by 20 percent viral replication from CD4+T cells isolated from patients with detectable amounts of virus in their bloodstreams.

The inhibitor works by binding tightly to the viral protein known as Tat, a potent activator of HIV gene expression, effectively preventing the virus from replicating even at miniscule concentrations—making it the most potent anti-Tat inhibitor described to date, Valente said.

Another interesting feature of this compound is that withdrawal of the drug from cell culture does not result in virus rebound, which is normally observed with other antiretrovirals.

While most antiretroviral compounds block only new infections, didehydro-Cortistatin A reduces viral replication from already-infected cells, potentially limiting cell-to-cell transmission.
The new inhibitor already has a drug-like structure, is effective at very low concentrations, and has no toxicity associated with it, at least at the cellular level, the study noted

The first author of the study “Potent Suppression of Tat-dependent HIV Transcription by didehydro-Cortistatin A” is Guillaume Mousseau of Scripps Research. In addition to Valente and Baran, other authors include Mark A. Clementz, Wendy N. Bakeman, Nisha Nagarsheth, Michael Cameron, and Jun Shi of Scripps Research; and Rémi Fromentin and Nicolas Chomont of the Vaccine and Gene Therapy Institute.

The study was supported by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) and the Landenberger Foundation.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, Scripps Research has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
For information:
Office of Communications
Tel: 858-784-8134
Fax: 858-784-8136
press@scripps.edu

Eric Sauter | EurekAlert!
Further information:
http://www.scripps.edu

Further reports about: CD4+T Scripps T cells cell death compound culture immune cell infected cells therapy viral replication

More articles from Life Sciences:

nachricht A landscape of mammalian development
21.02.2019 | Max-Planck-Institut für molekulare Genetik

nachricht Atopic dermatitis: elevated salt concentrations in affected skin
21.02.2019 | Technische Universität München

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Light from a roll – hybrid OLED creates innovative and functional luminous surfaces

Up to now, OLEDs have been used exclusively as a novel lighting technology for use in luminaires and lamps. However, flexible organic technology can offer much more: as an active lighting surface, it can be combined with a wide variety of materials, not just to modify but to revolutionize the functionality and design of countless existing products. To exemplify this, the Fraunhofer FEP together with the company EMDE development of light GmbH will be presenting hybrid flexible OLEDs integrated into textile designs within the EU-funded project PI-SCALE for the first time at LOPEC (March 19-21, 2019 in Munich, Germany) as examples of some of the many possible applications.

The Fraunhofer FEP, a provider of research and development services in the field of organic electronics, has long been involved in the development of...

Im Focus: Regensburg physicists watch electron transfer in a single molecule

For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.

The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...

Im Focus: University of Konstanz gains new insights into the recent development of the human immune system

Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens

Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...

Im Focus: Transformation through Light

Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light

When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...

Im Focus: Famous “sandpile model” shown to move like a traveling sand dune

Researchers at IST Austria find new property of important physical model. Results published in PNAS

The so-called Abelian sandpile model has been studied by scientists for more than 30 years to better understand a physical phenomenon called self-organized...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Global Legal Hackathon at HAW Hamburg

11.02.2019 | Event News

The world of quantum chemistry meets in Heidelberg

30.01.2019 | Event News

Our digital society in 2040

16.01.2019 | Event News

 
Latest News

A landscape of mammalian development

21.02.2019 | Life Sciences

Surprising findings on forest fires

21.02.2019 | Earth Sciences

Atopic dermatitis: elevated salt concentrations in affected skin

21.02.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>