LABORATORY INFORMATICS


Joining the computer-aided battle against antibiotic resistance


COMPUTATIONAL TOOLS FEATURE IN THE FIGHT AGAINST ANTIBACTERIAL RESISTANCE, WRITES CLAIRE SANSOM


Dame Sally Davies, the outgoing Chief Medical Officer for England, pulls no punches when it comes


to the threat of antibiotic resistance. She has called for an ‘Extinction Rebellion- type’ response to it, describing it as ‘catastrophic’ and ‘as dangerous as climate change’. And climate change makes a clear parallel with antibiotic resistance in another way: there has been progress in tackling it, but that progress is incremental and can seem glacially slow compared to the growing need. 2018 was something of a record year


for drug approvals at the FDA. It saw 42 new molecular entities (traditional ‘small- molecule’ drugs) and a further 17 new biological molecules, such as therapeutic antibodies for cancer, enter the clinic for the first time: the highest total since the agency started keeping count in 1993. However, relatively few of these were anti- infectives and only six were for bacterial infections. And, without exception, all these six were what is called ‘me too’ drugs: molecules in known chemical classes with known mechanisms of action. These generally confer only marginal clinical benefit over the drugs already available and, furthermore, bacteria can develop resistance to them in much less time than they do to drugs with completely new targets and mechanisms.


16 Scientific Computing World December 2019/January 2020


The extensive report that former UK prime minister David Cameron commissioned in 2014 from Jim O’Neill, was one of several initiatives earlier this decade to help kick-start such progress, as there has been, in combating resistant bacteria. Five years on, a progress report has listed nine current ‘ambitions for change’. The second of these, ‘drive innovation’, covers all aspects of drug discovery and development. And progress in innovation there has certainly been. In what is actually a largely pessimistic editorial, the director of the Wellcome Trust, Jeremy Farrar, highlighted the value of the ‘exciting crop of [small] biotechs that are now driving antibiotic innovation.’ A number of these focus on computer- based drug discovery methods. Since the last time this issue was covered in Scientific Computing World, just over 18 months ago, the companies featured there – Oxford Drug Design and Forge Therapeutics – have both been making steady progress.


Computational research University of Oxford spinout firm Inhibox became Oxford Drug Design (in 2017 when it changed its focus to designing drugs for antibiotic-resistant infections. Its rationale involves searching enormous compound databases for molecules that are likely to bind to target proteins, using novel algorithms that recognise molecular shape extremely fast. During 2019 it has received four large grants totalling more than £9m towards its two main drug discovery programmes, targeting the bacterial enzymes aminoacyl tRNA synthase and histidine kinase. ‘Our small office is devoted to computational work, and it is neither feasible, nor desirable, to apply these resources to expanding our servers and hiring informatics staff,’ says the company’s CEO, Paul Finn. ‘Instead, we expect to invest most of this welcome funding in work with contract research organisations to confirm – or otherwise – predictions made using our algorithms.’ The most recent of these grants came


@scwmagazine | www.scientific-computing.com


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