Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rutgers scientists discover molecules that show promise for new anti-flu medicines

04.10.2013
Chemicals block ability of flu virus to replicate in cells; goal is to develop medicines that fight much-feared pandemic influenzas

A new way to attack flu viruses is taking shape in laboratories at Rutgers University, where scientists have identified chemical agents that block the virus's ability to replicate itself in cell culture.


A chemical compound binds to and inhibits the active site of an enzyme that the influenza virus uses during replication.

Credit: Joseph D. Bauman

These novel compounds show promise for a new class of antiviral medicines to fight much-feared pandemic influenzas such as the looming "bird flu" threats caused by the H5N1 influenza A virus and the new H7N9 virus responsible for a 2013 outbreak in China.

Timely production of a vaccine is difficult when a pandemic flu strikes. A viable alternative is to treat with drugs.

"Right now there's really only one effective oral drug for treating influenza," said Eddy Arnold, professor of chemistry and chemical biology in the School of Arts and Sciences at Rutgers and a member of the Center for Advanced Biotechnology and Medicine. And just as bacteria develop resistance to antibiotics, Arnold notes that some flu strains have developed resistance to Tamiflu, the sole orally available anti-flu drug.

Arnold and his collaborators have been working to create drugs beyond Tamiflu, especially ones that target different parts of the virus, using an approach that helped in the development of powerful anti-AIDS drugs. By synthesizing chemical compounds that bind to metal ions in a viral enzyme, the researchers found they could halt that enzyme's ability to activate a key step in the virus's replication process.

In Arnold's words, his team's compounds "really gum up" the targeted enzyme of influenza virus.

"We're at a key proof of principle stage right now," he said. "It's not trivial to go from this point to actually delivering a drug, but we're optimistic – this class of inhibitors has all the right characteristics."

Rutgers' search for these binding compounds relies on technology that reveals the structure of this enzyme in extremely fine detail. Researchers Joseph Bauman and Kalyan Das first produced high-resolution images of an H1N1 flu enzyme, and Bauman and postdoctoral researcher Disha Patel screened 800 small molecule fragments for binding.

The researchers in Arnold's lab worked with Edmond LaVoie, professor and chair of medicinal chemistry in the Ernest Mario School of Pharmacy, to modify those compounds, making them more potent and selective in blocking the flu enzyme's activity. Working with virologist Luis Martinez-Sobrido at the University of Rochester, they were able to detect antiviral activity of the compounds in cells.

The enzyme that the scientists are attacking is especially crafty, Arnold noted, because it steals material from human cells to disguise the invading flu virus in a process called "cap-snatching." These "caps" are a small chemical structure that prime the process for reading genetic information."What we're doing by blocking or inhibiting this enzyme is to interefere with flu's ability to disguise itself," he said.

Arnold cited research by universities and pharmaceutical companies nearly two decades ago that took this approach, but initially the technology to obtain high-resolution images of the influenza protein wasn't available. One pharmaceutical company, Merck, later applied the approach of targeting metal-ion containing active sites in the HIV enzyme integrase and developed a highly successful anti-AIDS drug.

"It's truly remarkable what they did, and we're trying to pursue similar logic with influenza," said Arnold.

The researchers have recently published their findings in the American Chemical Society journal ACS Chemical Biology. Some of the work was funded by the National Institutes of Health. Two additional publications in the journals Bioorganic Medicinal Chemistry and ACS Medicinal Chemistry Letters have described LaVoie's synthetic medicinal chemistry used to make the new anti-flu agents and the observed structure-activity relationships.

Carl Blesch | EurekAlert!
Further information:
http://www.rutgers.edu

Further reports about: ACS Rutgers Tamiflu chemical engineering flu virus high-resolution image human cell

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>