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.
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Tom Bennett, BBSRC (Oct 2017), £523,679
Neil Ranson, Darren Tomlinson, BBSRC (Oct 2017), £494,318
Nikita Gamper, BBSRC (Oct 2017), £490,426
Amanda Bretman and colleagues from UEA, NERC (Oct 2017), £430,886
Juan Fontana, Rosetrees Trust consumables grant (Oct 2017), £22,500
Helen Miller, DSM Nutritional Products AG (Sep 2017), £69,988
Neil Ranson, Juan Fontana, Mark Harris, Michelle Peckham, Ralf Richter, Peter Stockley, Patricija Van Oosten-Hawle and colleagues in Engineering, FMH and MAPS, Wellcome Trust Equipment Call (Sep 2017), £418,000
Jamie Johnston, Physiological Society (Sep 2017), £10,000
Frank Sobott, Adrian Goldman, Mark Harris, Andrew Macdonald, Stephen Muench, Sheena Radford and colleagues in FMH and MAPS, Wellcome Trust Equipment Call (Aug 2017), £415,000
Ralf Richter, David Brockwell, Eric Hewitt, Jessica Kwok, Emanuele Paci and MAPS/FMH, BBSRC (Jun 2017), £600,000
Eric Blair, Adrian Whitehouse, Nicola Stonehouse, Alison Baker, Richard Bayliss, Joan Boyes, Ryan Seipke, Sally Boxall and MAPS/FMH, BBSRC (Jun 2017), £376,000
Stefan Kepinski, Yoselin Benitez-Alfonso, Tom Bennett, Michelle Peckham, BBSRC (Jun 2017), £331,000
Roman Tuma, Lars Jeuken, Paul Millner, Sheena Radford, Peter Stockley and MAPS/FMH, BBSRC (Jun 2017), £222,000
Vas Ponnambalam, Darren Tomlinson, Stephen Wheatcroft, BHF (May 2017), £107,878
Graham Askew in collaboration with Bangor University, BBSRC (Mar 2017), £477,383
Stephen Muench, BBSRC (Mar 2017), £132,945
Nic Stonehouse, MRC (Mar 2017), £906,341
Bill Kunin, Steve Sait, BBSRC (Mar 2017), £602,831
Adrian Goldman, EU (Mar 2017), £546,576
Sheena Radford, Wellcome Trust (Mar 2017), £1,836,482
Jamie Johnston, Royal Society (Mar 2017), £15,000
Beatrice Filippi, Royal Society (Mar 2017), £15,000
Tom Bennett, Royal Society (Mar 2017), £15,000
Ryan Seipke, BBSRC (Feb 2017), £52,116
Mary O'Connell, BBSRC (Feb 2017), £46,986
Hannah Dugdale, NERC (Feb 2017), £504,138
Anastasia Zhuravleva, EPSRC (Jan 2017), £100,792
Richard Bayliss, Cancer Research UK (Jan 2017), £1,600,000
John Barr, EU (Jan 2017), £339,000
Mark Harris, Royal Society (Jan 2017), £250,000
Alison Dunn, NERC (Jan 2017), £105,000
Alex Breeze, Pancreatic Cancer Research Fund (Jan 2017), £180,000
Alison Dunn, NERC (Dec 2016), £18,000
Lisa Collins, BBSRC (Dec 2016), £1,681,835
Brendan Davies, Leverhulme Trust (Dec 2016), £247,555
Alan Benson, Mark Drinkhill, Ed White, British Heart Foundaion (Dec 2016), £217,223
Adrian Goldman, Royal Society (Dec 2016), £82,999
Lisa Roberts, Alex Breeze, Brendan Davies, Timothy Devinney, Oliver Harlen, Joseph Holden, Anthea Hucklesby, Pamela Jones, Philip Mellor, RCUK (Nov 2016), £484,172
Lisa Roberts, Alex Breeze, Brendan Davies, Timothy Devinney, Oliver Harlen, Joseph Holden, Anthea Hucklesby, Pamela Jones, Philip Mellor, Wellcome Trust (Nov 2016), £119,343
Katie Field, Rank Prize Funds (Nov 2016), £20,000
Jessica Kwok, Royal Society (Nov 2016), £14,948
John Ladbury, Cancer Research UK (Oct 2016), £4,250
Miriam Wittmann, Martin Stacey, Edward Vital, Lupus UK
(Oct 2016), £34,010
Valerie Speirs, NC3Rs
(Oct 2016), £90,000
Nicola Stonehouse, Morgan Herod, David Rowlands, BBSRC
(Sep 2016), £436,424
Joseph Cockburn, Wellcome Trust
(Sep 2016), £100,000
John Barr, Public Health England
(Sep 2016), £94,471
Helen Miller, DSM Nutritional Products A/S
(Sep 2016), £54,680
Steven Clapcote, Vitaflo International Ltd
(Sep 2016), £39,285
Juan Fontana Jordan De Urries
, Royal Society
(Sep 2016), £21,793
Jing Li, Sarah Calaghan, Mark Drinkhill, British Heart Foundation
(Sep 2016), £117,585