Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

An approach to new antiviral medicines using a combination of genomics and proteomics

10.12.2015

World-wide recurrent seasonal influenza epidemic are mainly caused by influenza A viruses. However, these are frequently resistant to currently available antiviral medications. Scientists from the Paul-Ehrlich-Institut together with international research collaborators have identified a new target protein, which can be used to help develop novel antivirals in future. This was achieved by analysing the interactions between the influenza A virus and the infected cells in humans. Cell Host Microbe reports on these research results in its online edition of 9 December.

Between two and ten million people are infected with influenza viruses, that cause seasonal annual epidemics of disease. Influenza viruses are subdivided into influenza A, B, and C and their various subtypes. Influenza A viruses often constitute the main type of the circulating influenza viruses world-wide.


Human lung carcinoma cells infected with influenza A virus (nucleus in blue). The viral proteins haemagglutinin (green) and matrix protein 2 (red) are mainly located on the plasma membrane.

Source: Center for Microscopy and Image Analysis, University of Zurich

Influenza viruses undergo rapid genetic changes, therefore, influenza vaccines are adapted to the circulating seasonal influenza viruses each year. Moreover, drugs against influenza viruses, so-called antivirals, are required to treat infected individuals and are needed as a future treatment option for the occurrence of new (influenza) viruses – especially in the event of a pandemic. Meanwhile, however, a great number of influenza A viruses have become resistant to the currently available antiviral medications.

An approach to new effective antivirals against viruses is to inhibit the interaction between the virus and its host, i.e. the affected cells in the infected individual, since viruses use human cell proteins to reproduce and proliferate. A blockage of the interaction between virus proteins and cell proteins could inhibit the reproduction of the viruses, thus treating influenza successfully.

So far, the exact mechanism of interaction of influenza A virus with human cells have not been fully understood. Extensive systems-level data are available worldwide, but are seemingly discordant.

A joint collaborative research effort between four international research groups – including the group of Dr Renate König, head of the research team “Cellular Aspects of Pathogen-Host Interactions” at the Paul-Ehrlich-Institut have succeeded in generating a biochemical “map” of essential influenza A virus/host interactions. They achieved this by combining extensive genomic (relating to genes) and proteomic (relating to proteins) data analyses.

With the help of this map, the scientists identified UBR4 (ubiquitin protein ligase E3 component n-recognin 4), a protein in human cells which is responsible for “budding”, i.e. separating the viruses from the cell membrane, the exiting of the pathogen from the cell and subsequent proliferation within and outside the body. The scientists assume that UBR4 is “borrowed” by the virus to deactivate a protection mechanism in humans using its enzymatic function.

According to the scientists, this protection mechanism is as yet not known in detail. The scientists assume that it causes degradation of the viral proteins thus stopping them from being transported to the cell membrane. Based on this model, the influenza A virus thus buys itself a safe passage to the cell membrane. A novel approach to developing new antiviral drugs against the influenza A virus could be to strengthen the above mentioned protective mechanism.

“One advantage of active substances acting on cellular (human) proteins essential for the virus is the fact that the human genome does not constantly change so that active substances should also show long-term efficacy”, as Dr. König explains. Another advantage is that drugs that target cellular proteins may be effective against quite different viruses which utilize the same human protein machinery, of course, without disrupting essential cell functions. And finally, cellular proteins as target structures have the potential to be used to enhance the efficacy of vaccines.

Original publication

Tripathi S, Pohl MO, Zhou Y, Rodriguez-Frandsen A,, Wang G, Stein DA, Moulton HM, DeJesus P, Che J, Mulder LC, Yángüez E, Andenmatten D, Pache L, Manicassamy B, Albrecht RA, Gonzalez MG, Nguyen Q, Brass A, Elledge S, White M, Shapira S, Hacohen N, Karlas A, Meyer TF, Shales M, Gatorano A, Johnson JR, Jang G, Johnson T, Verschueren E, Sanders D, Krogan N, Shaw M, König R#, Stertz S#, García-Sastre A#, Chanda SK# (2015):
Meta- and Orthogonal Integration of Influenza ‘OMICs’ Data Reveals UBR4 as a Critical Regulator of M2 Ion Channel Membrane Trafficking. Cell Host Microbe. 2015 18: 723-735.
# Co-senior authors

The Paul-Ehrlich-Institut, the Federal Institute for Vaccines and Biomedicines, in Langen near Frankfurt/Main is a senior federal authority reporting to the Federal Ministry of Health (Bundesministerium für Gesundheit, BMG). It is responsible for the research, assessment, and marketing authorisation of biomedicines for human use and immunological veterinary medicinal products. Its remit also includes the authorisation of clinical trials and pharmacovigilance, i.e. recording and evaluation of potential adverse effects. Other duties of the institute include official batch control, scientific advice and inspections. In-house experimental research in the field of biomedicines and life science form an indispensable basis for the manifold tasks performed at the institute. The Paul-Ehrlich-Institut, with its roughly 800 members of staff, also has advisory functions nationally (federal government, federal states (Länder)), and internationally (World Health Organisation, European Medicines Agency, European Commission, Council of Europe etc.).

Weitere Informationen:

Publication Abstract
http://www.pei.de/EN/information/journalists-press/press-releases/2015/20-approa... - This press release on the PEI-Website

Dr. Susanne Stöcker | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

nachricht CWRU researchers find a chemical solution to shrink digital data storage
22.06.2017 | Case Western Reserve University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>