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.
Darren Tomlinson, Michelle Peckham, Megan Wright, BBSRC (Jun 2018), £150,443
Simon Walker, Royal Society (Jun 2018), £337,601
Tom Thirkell, N8 Agrifood (Jun 2018), £14,870
Stephen Muench with Glaxo SmithKline & UCB Celltech, BBSRC Industrial Partnership Award (Apr 2018), £480,225
Steve Clapcote, BBSRC (Apr 2018), £443,072
Helen Miller, Innovate UK (Apr 2018), £999,960
Elisabetta Groppelli, David Rowlands & Stanley Lemon (University of North Carolina), Medical Research Foundation Fellowship (Apr 2018), £293,494
Nikesh Patel, Medical Research Foundation fellowship (Apr 2018), £290,976
Graham Askew with colleagues in Hull and Liverpool, BBSRC (Apr 2018), £150,498
Andrew Macdonald, Neil Ranson & Richard Foster, Kidney Research UK (Apr 2018), £82,821
Jessica Kwok & Ralf Richter, Leverhulme Trust (Apr 2018), £298,273
Julie Aspden, Royal Society (Apr 2018), £20,000
Liz Duncan, Royal Society (Mar 2018), £14,602
Alex O'Neill & Ryan Seipke, BBSRC (Feb 2018), £45,489
Jim Deuchars, Royal Society (Feb 2018), £16,300
Stefan Kepinski & Netta Cohen, Leverhulme Trust (Feb 2018), £320,387
Lisa Collins, BBSRC (Feb 2018), £49,950
Alison Baker, BBSRC (Feb 2018), £30,000
Lars Jeuken, BBSRC (Feb 2018), £30,000
Nikita Gamper, BBSRC (Feb 2018), £30,000
Scott Bowen, Leducq Foundation Grant (Feb 2018), £28,470
Jessica Kwok and Ronaldo Ichiyama, International Spinal Research Trust (Feb 2018), £94,450
Alex O'Neill, Oxford Drug Design (Jan 2018), £86,098
Dave Lewis and Colleagues in South Africa, HEFCE Global Challenge Research (Jan 2018), £48,000
Sarah Calaghan, Ed White, John Colyer, Isuru Jayasinghe, BHF (Jan 2018), £128,308
Christine Foyer and Alison Baker, HEFCE GCRF Grant (Jan 2018), £71,158
Alison Baker, Yun Yung Gong and Lindsay Stringer and ICRISAT India, HEFCE GCRF Grant (Jan 2018), £27,000
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Alison Dunn, NERC (Dec 2017), £18,000
Jennifer Tomlinson, Royal Society-Research Fellows Enhancement Award (Dec 2017), £94,681
Helen Miller, AB AGri Grant (Dec 2017), £73,600
Simon Walker, Royal Society Enhancement Award (Dec 2017), £10,000
Carrie Ferguson, Bryan Taylor, Harry Rossiter, The Physiological Society (Dec 2017), £7,392
Ralf Richter, Royal Society (Dec 2017), £6,000
Christine Foyer, British Council Newton Fund (Dec 2017), £49,840
Adrian Whitehouse and colleagues in School of Chemistry and University of Liverpool, MRC (Nov 2017), £622,319
Michelle Peckham, Neil Ransom, MRC (Nov 2017), £495,159
Dave Lewis, British Council India (Nov 2017), £22,540
Hannah Dugdale, Royal Society (Nov 2017), £15,000
Elton Zeqiraj, Royal Society (Nov 2017), £15,000
Shaunna Burke, Cancer Research UK Innovation Grant (Nov 2017), £20,000
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Jessica Kwok, Wings for Life (Nov 2017), £87,365
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