'Rational drug design' identifies fragments of FDA-approved drugs relevant to emerging viruses

Dec 06, 2009

A massive, data-crunching computer search program that matches fragments of potential drug molecules to the known shapes of viral surface proteins has identified several FDA-approved drugs that could be the basis for new medicines -- if emerging viruses such as the H5N1(avian flu) or H1N1/09 (swine flu) develop resistance to current antiviral therapies -- according to a presentation at the American Society for Cell Biology 49th Annual Meeting, Dec. 5-9, 2009 in San Diego.

The compounds were identified through a "rational drug design" project in the laboratory of Andrew McCammon, Ph.D., HHMI investigator at the University of California at San Diego.

The McCammon lab honed the search algorithms that helped identify the second generation of anti-HIV drugs.

Like fitting a key to a lock, computer search algorithms take the known shapes of drugs and match them, one after another, to the known shapes of disease-related proteins.

In the study presented at the ASCB conference, Daniel B. Dadon, a member of the McCammon lab, will explain how the search targeted the neuraminidase proteins, one of the two major sets of glycoproteins on the outer surface of influenza viruses.

Because biomolecules don't sit still -- they're moving targets -- scientists must consider how the protein can slightly shift position or shape. Dadon said, "A single picture of a sleeping cheetah, for example, might suggest that the animal is always lethargic. In reality, a cheetah is dynamic, spending much of its time sitting, running, climbing, attacking, and walking."

The successful capture of cheetahs or influenza viruses requires an understanding of their motions over time.

A search algorithm that accounts for the flexibility of the molecular docking sites is at the core of the McCammon group's relaxed complex scheme (RCS).

After studying neuraminidase flexibility, the researchers created a virtual library of drug-like molecules by mixing and matching parts of various FDA-approved drugs.

The information gained from the RCS simulations was used to identify molecules in this new library that would best inhibit neuraminidase function.

Six compounds were predicted to inhibit neuraminidase better than FDA-approved drugs such as oseltamivir, peramivir and zanamivir.

The computer data also suggests that some of these compounds may target other parts of the neuraminidase protein. The ability to target these additional parts of the protein could prove useful if the new viruses develop resistance to current therapies.

Source: American Society for Cell Biology

Explore further: Novel marker discovered for stem cells derived from human umbilical cord blood

add to favorites email to friend print save as pdf

Related Stories

A New Way of Treating the Flu

Jun 13, 2009

What happens if the next big influenza mutation proves resistant to the available anti-viral drugs? This question is presenting itself right now to scientists and health officials this week at the World Health ...

A New Way of Treating the Flu

Jul 06, 2009

(PhysOrg.com) -- What happens if the next big influenza mutation proves resistant to the available anti-viral drugs? This question was presenting itself to scientists and health officials recently at the World ...

Virtual screening leads to real progress in drug design

Oct 28, 2008

Around 150,000 people per year get African sleeping sickness, a disease spread by the biting tsetse fly and caused by the parasite Trypanosoma brucei. Unless treated, the illness is invariably fatal. And ...

Recommended for you

New pain relief targets discovered

2 hours ago

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

Building 'smart' cell-based therapies

2 hours ago

A Northwestern University synthetic biology team has created a new technology for modifying human cells to create programmable therapeutics that could travel the body and selectively target cancer and other ...

Proper stem cell function requires hydrogen sulfide

5 hours ago

Stem cells in bone marrow need to produce hydrogen sulfide in order to properly multiply and form bone tissue, according to a new study from the Center for Craniofacial Molecular Biology at the Herman Ostrow School of Dentistry ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

FGHafler
not rated yet Dec 09, 2009
Thank you for writing this article. It really opened up my eyes to your point of view. I was looking for more advice for my own medical needs and found this. Allthough it was not what I was looking for I did find it easy to read and captivating. I was looking for advice on a new medicine. I am using this Mexican pharmacy for my needs as they are owned and run by Americans whom I have grown to trust but I find it hard to get advice unless I see the doctor. Anyway I have gone a bit off topic and want to just thank you for your article.

More news stories

Researchers discover target for treating dengue fever

Two recent papers by a University of Colorado School of Medicine researcher and colleagues may help scientists develop treatments or vaccines for Dengue fever, West Nile virus, Yellow fever, Japanese encephalitis and other ...

Study recalculates costs of combination vaccines

One of the most popular vaccine brands for children may not be the most cost-effective choice. And doctors may be overlooking some cost factors when choosing vaccines, driving the market toward what is actually a more expensive ...

Hackathon team's GoogolPlex gives Siri extra powers

(Phys.org) —Four freshmen at the University of Pennsylvania have taken Apple's personal assistant Siri to behave as a graduate-level executive assistant which, when asked, is capable of adjusting the temperature ...

Better thermal-imaging lens from waste sulfur

Sulfur left over from refining fossil fuels can be transformed into cheap, lightweight, plastic lenses for infrared devices, including night-vision goggles, a University of Arizona-led international team ...

Deadly human pathogen Cryptococcus fully sequenced

Within each strand of DNA lies the blueprint for building an organism, along with the keys to its evolution and survival. These genetic instructions can give valuable insight into why pathogens like Cryptococcus ne ...