July 19th, 2012 by Michael Ricciardi
A collaborative research team at the Scripps Research Institute in Florida have successfully concluded experiments on HIV infected cell cultures using a derivative of a natural compound called Cortistatin A which was isolated in 2006 from a sea sponge called Corticium simplex that was first identified over a hundred years ago.
The compound was first synthesized in 2008 by a Scripps research team lead by Phil Baran. Baran’s lab collaborated in this breakthrough research.
In the study (by Mousseau et al), a synthetic version of the compound called didehydro-Cortistatin A was used to test its effects on two a forms of HIV — HIV-1 (the most common form) and HIV -2 (a form restricted to W. Africa and part of Europe).
Results of the in vitro experiments showed a 99.7 % reduction in the viral production (replication) from immune cells known as primary CD4+ T cells. These cells had been previously isolated from patients undergoing a prolonged, anti-retro-viral therapy, known as HAART, and without any detectable signs of the virus in their blood.
Further, in patients with detectable loads of the virus in their blood, it was found that combining the compound with other antiviral medications resulted in an additional 20% reduction in viral replication from this same population of T cells.
Unlike other antiviral drugs help block new infections, this nature-derived compound stops the virus in cells that are already infected. Currently, it is estimated that 34 million people world-wide are infected with either strain of HIV, the virus known to cause AIDS.
The potent inhibitory mechanism apparently works by binding strongly to a viral protein called Tat which promotes activation of the viral genes. this binding effect “gums up” the replication machinery of the virus — inhibiting even small amounts of replication. The team leader Susana Valente described the compound as “the most potent anti-Tat inhibitor described to date.”
And while cell culture, or in vitro, studies are never definitive — natural cell tissue (in vivo) exist in micro environments that relay all manner of signals from their surroundings — the researchers are more than a little confident in this new compound.
Two features of this compound are giving medical researchers additional hope: first, removal of the compound from the cell cultures does not result in a “rebound” of the viral infection and second, the compound has a “drug-like” molecular structure (i.e., a strongly conserved binding site), and so, it is ready-made for antiviral therapeutics.
Additionally, it works at low concentrations and appears to have zero toxicity at the cellular level.
The study (“Potent Suppression of Tat-dependent HIV Transcription by didehydro-Cortistatin A”) was published July 20, 2012 issue of the journal Cell Host and Microbe and was supported by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) and the Landenberger Foundation. Additional researchers 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.
Top image: CDC – Scanning electron micrograph of HIV-1 (in green) budding from cultured lymphocyte. Multiple round bumps on cell surface represent sites of assembly and budding of virions.
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