The battle against AIDS cannot be won in the laboratory alone. To fight the potentially deadly virus that 34 million people are suffering from we need help from computers. Now research fron University of Southern Denmark turns computers into powerful allies in the battle.
Effective treatment of HIV-virus is a race against time: Many of the drugs that have been potent killers of HIV-virus, have today lost their power, because the virus has become resistant to them. As a result science must constantly develop new drugs that can attack the virus in new ways.
Now researchers from the University of Southern Denmark present a method to speed up the important development work up with an order of several hundred percent.
It now takes not years, but months or even only weeks to find new compounds that have the potential to become a new HIV drug. Finding suitable compounds that can specifically inhibit the HIV virus, is crucial in AIDS research, explains postdoc Vasantanathan Poongavanam from Department of Physics, Chemistry and Pharmacy, University of Southern Denmark:
"HIV is a retrovirus that contains enzymes which make it able to copy itself with the help of host genetic material and thus reproduce. If you can block these enzymes’ ability to replicate itself, the virus cannot reproduce."
The needle in the haystack
An almost infinite number of different substances can be synthetized in a laboratory. Some of them may prove to inhibit HIV-virus’s reproduction, but finding them is like finding a needle in a haystack.
"It takes enormous amounts of time and resources, to go through millions and millions of compounds. With the techniques used today, it may take years to carry out a screening of possible compounds”.
In addition, it takes time to turn an effective compound into a safe pharmaceutical agent that can get on the market.
"Today, it generally takes nearly 14 years from the time you find a drug candidate to get it on the market. Anything that can shorten that time is an important improvement”, says Vasanthanathan Poongavanam.
Until now, researchers have been hampered by slow computers and inaccurate prediction models when they ask computers to identify compounds that may be effective against HIV. Now the SDU researchers have managed to develop an effective model at a time when significantly more powerful computers have become available.
“Our work shows that computer based predictions are a extremely fast, accurate and promising methodology in the drug discovery projects”, says Vasanthanathan Poongavanam.
14 new compounds found
With the new methods based on quantum mechanics and molecular mechanics, Vasanthanathan Poongavanam and his colleague, Jacob Kongsted, screened half a million compounds and found 25 that were interesting to investigate further. These 25 were tested in a conventional laboratory experiment, and 14 of them were found to inhibit HIV virus's ability to reproduce.
"It took us only a few weeks to find these 14 very interesting compounds, whereas before it would have taken years", explains Vasanthanathan Poongavanam.
The 14 compounds have now been taken over by Italian researchers who continue working with them at the University of Cagliari. The next step is to carry out advanced experiments on these compounds. If they are positive, the compounds may go on the market as a drug against HIV.
Illustration HIV virus (big purple balls) are entering a host cell. Once they have entered, they deliver their cargo of viral RNA (purple capsule looking container). The container also carries enzymes needed for the virus to copy itself, and the goal is to inhibit these enzymes so that the virus no longer can copy itself.
The description of the new method are published in the journals Integrative Biology and Plos One.
Ref: Binding free energy based structural dynamics analysis of HIV-1 RT RNase H-inhibitor complexes. Vasanthanathan Poongavanam, Jógvan Haugaard Magnus Olsen, Jacob Kongsted. DOI: 10.1039 / C4IB00111G.
Inhibitor Ranking Through QM based Chelation Calculations for Virtual Screening of HIV-1 RNase H inhibition, Vasanthanathan Poongavanam, Casper Steinmann, Jacob Kongsted, PLoS ONE 9(6): e98659. doi:10.1371/journal.pone.0098659
Contact Postdoc Vasanthanathan Poongavanam, firstname.lastname@example.org. Tel: +45 65502570. Mobile: +45 23377705.
Birgitte Svennevig | Eurek Alert!
GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University
Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy