Sprint 1: Started Sun Jul 26 06:31:13 UTC 2020
We are an international group of scientists from academia and industry trying to do our small part to help combat COVID-19. This effort began when Chinese scientists worked rapidly to determine the structure of the novel SARS-CoV-2 main protease (Mpro), which triggered a massive crystal-based fragment screen at the XChem facility at UK’s Diamond Light Source. With the same urgency, we are now trying to progress these data towards what is desperately needed: effective, easy-to-make anti-COVID drugs.
We welcome contributions of many forms including scientific expertise, experimental capabilities, and indeed donations to make this possible.
If you are an experimentalist with hands to lend, especially a Virologist with live assays, please email us. If you wish to make a financial contribution to help make and test more compounds, please see our donation page. If you have expertise in designing compounds, please keep reading and submit your designs below.
The XChem screening experiment at Diamond, combined with a mass spectrometry screen of covalent fragments in the London Lab at the Weizmann Institute (Israel), is detailed here, and yielded over 60 fragment hits directly with structures of fragment-protein complexes. All data are available from the website, as are links to interactive 3D views on the Fragalysis Cloud platform, where you can easily visualise in 3D all the fragment hits, covalent or non-covalent.
We are now asking for your help in designing new inhibitors based on these initial fragment hits: the exceptionally dense readout suggests countless opportunities for growing and merging, and we need many sharp brains to sift through them; it is also what makes us believe that potency can be directly achieved.
We encourage chemists to ideally focus on the active site of the target (sites 1, 8, 11 in Fragalysis), but if you have any reasons to favour a hit in adjacent sites and specify the rationale for it your compounds will be considered. We are most interested in creative fragment merges, but designs will be prioritized by numerous factors including ease of synthesis, and toxicity modeling. Compounds will then be synthesized by Enamine and tested by groups around the world. PostEra will be running machine learning algorithms in the background to triage suggestions and generate synthesis plans to enable a rapid turnaround. You will be informed of the progress of the molecules through the main stages (validation, synthesis and testing).
If you need access to computational resources or wish to request/offer help from/to others, please see the forum. Additionally, BioSolveIT has been kind enough to offer their SeeSAR software for free to our users for 30 days [see details].