Open Source Antibiotics Paper Number 1 #8
Description
Open Source Antibiotics (OSA) began in November 2018 with a coffee in the Green Building at the Old Road site at the University of Oxford. I was talking to Paul Brennan and Frank von Delft about taking fragment hits to lead compounds - there were few good examples of this back then - and we thought we should get something going. I suggested we open things up to the community. That project became the first project of OSA and is focussed on the mur ligases. Though we've very cool recent data on that project, we never (despite the best efforts of my talented postdoc at the time, Fahima Idris) got the fragments to go anywhere, but that's a different (and ongoing) story.
Though we were busy making the economic/policy argument about the value of open source methods for new antibiotic development (essentially, there is no market, so let's open it up) I was thinking we should start a second OSA series. One of the great potential benefits of a really open approach is its ability to immortalise teenage projects: work that has gone pretty far, and has obvious promise, but that is not yet fully mature. Let's say you have a series you're working on that looks OK but you either can't raise money or you can't quite get the potency high enough, or you have other things that are more pressing. You can't publish the work, and you think that you need to head off in a different direction. Do you just dispose of the data and forget all about it? Why not put the data (and your ideas) somewhere that other people can work on it all? Maybe someone out there has an idea, or can raise some funds, to take things to the next step. Immortalisation.
Just such a thing happened to OSA, and Series 2 was born. 3 years later, it's published.
The project started with a mail from Bill Zuercher, then at UNC Chapel Hill. He and the team there had evaluated a bunch of molecules they'd found in another project against bacteria, using CO-ADD as their screening resource. The data looked interesting and worth exploring. I managed to get a grant from something called Pharmalliance, which is a coalition of the pharmacy schools from UCL, UNC and Monash. We worked for a while doing some resynthesis and basic analog synthesis towards some kind of SAR.
The notable thing about this project was the feature we've often seen in projects of this kind, whereby a funded core in an open science project can attract contributors, in this case really valuable expertise from academia (Lori Ferrins from Northeastern as an excellent example), Industry (Hypha Discovery who worked with us on metabolite ID), NGOs (thank you, DNDi) consultancy (the ever-wise Chris Swain) and the public (citizen scientist Anthony Sama).
The regular meetings over the course of the pandemic were a real pleasure to run and record and helped keep everyone connected and on the same page.
These are interesting compounds which still have promise. Though we've stopped the project (in part, as always, through not having further funding) the project remains ready to re-activate. If you're a PhD or Masters student wanting something cool to work on, you could extend what we've done in full knowledge that you're in possession of all the facts and would not be unintentionally duplicating something we did that did not go anywhere. If you wanted to do the next key experiments, some of which we list at the end of the paper, you'd be more than welcome (the licence is CC-BY-4.0, so you don't need to ask permission - just cite your source) and you could use the data we've generated as the basis for your application for more resources. On a personal note I was frustrated that we never managed to figure out the bacterial protein target. I'd love to know what that is!