Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Identifying the mechanism for a new class of antiviral drugs could hasten their approval

25.10.2017

New research shows that a new class of antiviral drugs works by causing the virus' replication machinery to pause and backtrack, preventing the virus from efficiently replicating. This discovery, made possible by a high-throughput experimental technique called "magnetic tweezers," could speed the development and approval of related antiviral drugs. A paper describing the research by an international collaboration of scientists from Penn State University, Delft University of Technology in the Netherlands, Friedrich-Alexander University in Germany, and the University of Minnesota, appears October 24, 2017 in the journal Cell Reports.

"Viruses are a massive threat to global public health," said Craig Cameron, professor and holder of the Eberly Family Chair in Biochemistry and Molecular Biology at Penn State and an author of the paper.


The mechanism of a new class of antiviral drug. The RNA polymerase enzyme (yellow) replicates the virus genome by incorporating one nucleotide (black) at a time. Nucleotide analogues (red) are designed as antiviral drugs that can disrupt the replication process. The antiviral drugs work by (1) incorporating mutations, (2) stopping the replication process, or (3) a newly discovered mechanism in which the RNA polymerase enzyme pauses and then backtracks.

Credit: Penn State

"Developing broad-spectrum antiviral drugs -- ones that are effective against many different viruses -- is vital to our ability to prevent or respond to outbreaks. We were able to demonstrate the mechanism of a newly developed class of antiviral drugs that are potentially broad spectrum."

Essentially all viruses, whose genomes are composed of RNA rather than DNA, use an enzyme called RNA-dependent RNA polymerase to express genes and replicate their genome in order to make new copies of themselves. The polymerase enzyme is therefore an attractive target for developing broad-spectrum antivirals.

"In order to make more viruses, the RNA polymerase enzyme replicates the virus genome by incorporating nucleotides -- the building blocks of RNA or DNA, which are made up of a base and a sugar -- one at a time," said Jamie J. Arnold, an associate research professor at Penn State and another author of the paper.

"For many antiviral drugs, alternative versions of these building blocks are designed such that when they are incorporated during replication, they somehow disrupt the process. To understand the disruption mechanism, we used magnetic tweezers that allowed us to monitor the progression of hundreds of individual RNA polymerase enzymes during the replication process in the presence of antiviral drugs."

The magnetic tweezers work by tethering one end of hundreds of individual strands of RNA to a surface and attaching a magnetic bead to the other end. A magnet then holds the strands vertically while the researchers monitor the beads under a microscope.

As the RNA polymerase builds new RNA, the length of the strand changes, moving the bead up or down. Because they can monitor hundreds of these processes simultaneously, the researchers are able to build datasets and develop sound statistical backing for their observations.

"We were particularly interested in an antiviral called T-1106," said Cameron. "It is related to Favipiravir, which was recently approved in Japan for use in the treatment of influenza, but the mechanism was unknown. We were able to show that these antivirals -- a new class that alters the base of the RNA building block, rather than the sugar -- work in a new way.

Unlike other known antivirals that either incorporate mutations into the replication process or stop it completely, this new class works by causing the RNA polymerase enzyme to pause and backtrack. With this understanding, we can begin to fine tune the design of these antivirals and speed up the process of getting them approved."

###

In addition to Cameron and Arnold, the research team included Hyung-Suk Oh and Cheri Lee at Penn State; Nynke H. Dekker, Theo van Laar, and Martin Depken at Delft University of Technology; David Dulin of Delft University of Technology and the Friedrich-Alexander University; and Angela L. Perkins and Daniel A. Harki at the University of Minnesota.

The research was supported by the U.S. National Institute of Allergy and Infectious Disease of the National Institutes of Health, the Burroughs Wellcome Fund, the Netherlands Organisation for Scientific Research, and a European Union ERC Consolidator Grant.

Media Contact

Barbara Kennedy
BarbaraKennedy@psu.edu
814-863-4682

 @penn_state

http://live.psu.edu 

Barbara Kennedy | EurekAlert!

Further reports about: DNA Molecular Biology RNA RNA polymerase antiviral antiviral drugs enzyme viruses

More articles from Life Sciences:

nachricht Algae-killing viruses spur nutrient recycling in oceans
18.07.2019 | Rutgers University

nachricht How are pollen distributed in the air?
18.07.2019 | Leibniz-Institut für Troposphärenforschung e. V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First-ever visualizations of electrical gating effects on electronic structure

Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.

Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

Im Focus: Extremely hard yet metallically conductive: Bayreuth researchers develop novel material with high-tech prospects

An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".

The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...

Im Focus: Modelling leads to the optimum size for platinum fuel cell catalysts: Activity of fuel cell catalysts doubled

An interdisciplinary research team at the Technical University of Munich (TUM) has built platinum nanoparticles for catalysis in fuel cells: The new size-optimized catalysts are twice as good as the best process commercially available today.

Fuel cells may well replace batteries as the power source for electric cars. They consume hydrogen, a gas which could be produced for example using surplus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Genetic differences between strains of Epstein-Barr virus can alter its activity

18.07.2019 | Health and Medicine

Algae-killing viruses spur nutrient recycling in oceans

18.07.2019 | Life Sciences

Machine learning platform guides pancreatic cyst management in patients

18.07.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>