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

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Storage & Transport of highly volatile Gases made safer & cheaper by the use of “Kinetic Trapping"

Augsburg chemists present a new technology for compressing, storing and transporting highly volatile gases in porous frameworks/New prospects for gas-powered vehicles

Storage of highly volatile gases has always been a major technological challenge, not least for use in the automotive sector, for, for example, methane or...

Im Focus: Disrupting crystalline order to restore superfluidity

When we put water in a freezer, water molecules crystallize and form ice. This change from one phase of matter to another is called a phase transition. While this transition, and countless others that occur in nature, typically takes place at the same fixed conditions, such as the freezing point, one can ask how it can be influenced in a controlled way.

We are all familiar with such control of the freezing transition, as it is an essential ingredient in the art of making a sorbet or a slushy. To make a cold...

Im Focus: Micro energy harvesters for the Internet of Things

Fraunhofer IWS Dresden scientists print electronic layers with polymer ink

Thin organic layers provide machines and equipment with new functions. They enable, for example, tiny energy recuperators. In future, these will be installed...

Im Focus: Dynamik einzelner Proteine

Neue Messmethode erlaubt es Forschenden, die Bewegung von Molekülen lange und genau zu verfolgen

Das Zusammenspiel aus Struktur und Dynamik bestimmt die Funktion von Proteinen, den molekularen Werkzeugen der Zelle. Durch Fortschritte in der...

Im Focus: Dynamics of individual proteins

New measurement method allows researchers to precisely follow the movement of individual molecules over long periods of time

The function of proteins – the molecular tools of the cell – is governed by the interplay of their structure and dynamics. Advances in electron microscopy have...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

5th International Conference on Cellular Materials (CellMAT), Scientific Programme online

02.10.2018 | Event News

Major Project: The New Silk Road

01.10.2018 | Event News

"Boston calling": TU Berlin and the Weizenbaum Institute organize a conference in USA

21.09.2018 | Event News

 
Latest News

Physics: Not everything is where it seems to be

15.10.2018 | Physics and Astronomy

Microfluidic molecular exchanger helps control therapeutic cell manufacturing

15.10.2018 | Life Sciences

Link between Gut Flora and Multiple Sclerosis Discovered

15.10.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>