A team from the University’s schools of Chemistry and Molecular and Cellular Biology have secured a £200,000 grant from the Wellcome Trust to find drugs to cure the disease.
Although several Ebola vaccines are being developed, there are currently no effective anti-viral drugs to treat people once they get infected.
This is a particularly serious issue because of barriers to implementing vaccine programmes in the most at-risk communities and because of the difficulty of predicting where the disease will strike next. The University of Leeds researchers will focus on finding anti-viral drugs.
Instead of the traditional approach of biologically testing hundreds of candidate drug compounds in the lab, the researchers will run computer software loaded with a library of about one million drug compounds and match them against the atomic structure of the Ebola virus’s key proteins.
The second phase of the project will then test the most promising compounds to see if they inhibit Ebola-like molecules in biological tests.
Professor Mark Harris, Professor of Virology at the University of Leeds, who is leading the project, said: “Much of the scientific activity following the recent Ebola outbreak has focussed on repurposing existing drugs or developing vaccines. We are going back to the structure of the Ebola proteins to identify compounds that could be the basis of specially designed antivirals for Ebola.”
Professor Colin Fishwick, Professor of Medicinal Chemistry at the University of Leeds, will lead the computer-based phase of the study. He said: “The use of the computer hugely increases our ability to identify the right compounds. It is a bit like trying to crack a password by brute-force: we are able to run through hundreds of thousands of drug compound structures to see if they fit into key ‘holes’ we have identified in the structure of the virus.
“However, our computers are not dealing with strings of characters but minutely detailed 3D maps of molecules. We are matching key atomic details of the compounds and virus molecules and looking for chemicals that might block the virus’ growth and replication. It is an incredibly powerful system that transforms our ability to rapidly identify new drug leads.”
A team led by Professor Harris and Dr John Barr, an expert in Ebola-type viruses based in the University's School of Molecular and Cellular Biology, will then take the best candidate chemicals into biological tests.
Dr Barr explained: “In these biological assays, we will using non-infectious molecules that replicate key features of the Ebola virus’ structure and lifecycle. Useful compounds could then be tested on Ebola itself at Category Four containment facilities like Porton Down or Marburg in Germany.”
The project is looking for anti-viral drugs capable of combatting Ebola in infected patients, rather than vaccines.
Professor Harris said: “There are quite a few vaccines in various stages of development at the moment and some seem to be very promising. However, even if we do have a very successful vaccine for Ebola, we are going to need anti-virals. Getting enough vaccines to people in the communities most at risk from Ebola will be very difficult indeed. We already struggle with established vaccines like polio in some of these areas.
“It is important to stress that we are at the very early stages of identifying possible drug compounds, but this work could be the basis for new drugs for infected patients, much like people with flu can be treated with Tamiflu or HIV patients receive antiretrovirals.”
The study will focus on two key components of the Ebola virus: its NP and VP30 proteins. The atomic structures of both have been mapped in high resolution and both are known to be critical to the virus’ replication and growth. Two other proteins—the L and VP35 proteins—will also be studied by the team, which also includes Dr Thomas Edwards, an expert in protein structure, and Dr Richard Foster, a medicinal chemist. All of the researchers are members of The Astbury Centre for Structural Molecular Biology, which brings together scientists from across the University of Leeds to allow interdisciplinary approaches to understanding the molecular basis of life.
Stefan Kepinski, Michelle Peckham, BBSRC (Apr 2016), £461,760
David Brockwell, Sheena Radford, BBSRC (Apr 2016), £358,570
Ryan Seipke, BBSRC (Apr 2016), £340,536
Neil Ranson, Mark Harris, Ade Whitehouse, Peter Stockley, Sheena Radford, Alan Berry, Wellcome Trust (Mar 2016), £1,000,000
Thomas Edwards and colleagues in the School of Chemistry, EPSRC (Feb 2016), £2,228,732
Mark Harris, Thomas Edwards, John Barr and colleagues from the School of Chemistry, Wellcome Trust (Jan 2016), £204,959
Katie Field, BBSRC (Jan 2016), £830,381
Alan Berry, Alex Breeze, Adam Nelson, BBSRC (Jan 2016), £479,490
Paul Knox, BBSRC (Jan 2016), £40,000
Joe Cockburn, Royal Society (Dec 2015), £14,960
Katie Field, Royal Society (Dec 2015), £14,700
Stephanie Wright, Kay Kendall Leukaemia Fund (Dec 2015), £207,286
Zahra Timsah, Royal Society (Nov 2015), £15,000
Jessica Kwok, Wings For Life Spinal Cord Research (Nov 2015), £134,981
Alan Berry, Wellcome Trust (Oct 2015), £752,365
Julie Aspden, MRC (Oct 2015), £633,020
Steve Sait, NERC (Oct 2015), £386,061
Urwin, Howard Atkinson, BBSRC (Oct 2015), £200,293
Eric Hewitt, Andrew Macdonald, Yorkshire Kidney Research Fund (Oct 2015), £46,621
Dave Westhead, Bloodwise (Sep 2015), £664,109
Ade Whitehouse, Alison Ashcroft, Ian Carr, BBSRC (Sep 2015), £438,975
Shaunna Burke, Andrea Utley, Sarah Astill, Arts Council of England (Sep 2015), £80,594
Samit Chakrabarty, Ronaldo Ichiyama, Intl Foundn for Research in Paraplegia (Aug 2015), £93,000
Helen Miller, Agriculture & Horticulture Develpmnt Brd (Aug 2015), £63,560
Tim Benton, M & W MACK LTD (Aug 2015), £48,711
Eileen Ingham, John Fisher, EPSRC (Jul 2015), £1,458,439
Anastasia Zhuravleva, BBSRC (Jul 2015), £483,019
Alex O'Neill, MRC (Jul 2015), £249,822
Ade Whitehouse, Richard Foster, Cancer Research UK (Jul 2015), £201,034
Ronaldo Ichiyama, Jim Deuchars, Sue Deuchars, Wings For Life Spinal Cord Research (Jul 2015), £123,895
Helen Miller, ABNA Ltd (Jul 2015), £22,968
Martin Stacey and colleagues in FMH, MRC (Jun 2015), £426,475
Adrian Goldman, Sarah Harris, Roman Tuma, BBSRC (Jun 2015), £420,693
Elwyn Isaac, EU (Jun 2015), £238,915
Christine Foyer, BBSRC (Jun 2015), £160,401
Adrian Goldman, EU (Jun 2015), £116,331
David Brockwell, Sheena Radford, Innovate UK (Jun 2015), £113,378
Yoselin Benitez-Alfonso, EPSRC (Jun 2015), £93,672
Michelle Peckham, Peter Knight, Thomas Edwards, BBSRC (May 2015), £404,987
Michelle Peckham, Ed White, Peter Knight, BHF (May 2015), £208,184
Dave Westhead, Sheena Radford, Alex Breeze, BBSRC (May 2015), £51,021
Steve Clapcote, Vitaflo International Ltd (May 2015), £33,703
Les Firbank, Joe Holden, Pippa Chapman, NERC (Apr 2015), £388,726
Samit Chakrabarty, David Steenson, BBSRC (Apr 2015), £120,103
Paul Millner, Gin Jose, Sarah Aickin, DSTL Porton Down (Apr 2015), £63,407
Chris Hassell, David Lewis, The Physiological Society (Apr 2015), £6,900
Andrew Tuplin, Royal Society (Mar 2015), £15,000
Yoselin Benitez-Alfonso, Royal Society (Mar 2015), £14,770
Patricija Van Oosten-Hawle, Royal Society (Mar 2015), £13,960
Stuart Egginton, BHF (Mar 2015), £272,979
Keith Hamer, Department of Energy & Climate Change (Mar 2015), £58,066
Andrew Macdonald, Yorkshire Kidney Research Fund (Mar 2015), £41,171