SARS-CoV-2 - part 1 - Thriving for a systematic target and hit ID effort
As many of you, I’m writing these lines from home trying to juggle between work, childcare & teaching, household and a healthy state of mind.
Gabriella outlined in previous posts (part I & part II) a few things about SARS-CoV-2. Back at the time the crisis was still far away from our daily lives but things have changed dramatically during the last weeks. After our initial communication to make 3decision freely available for all Covid-19 related collaboration projects we were contacted independently by several volunteers from academic and industrial groups to collaborate on a global effort. At the same time a lot of novel initiatives have seen the day and everybody is publishing blog posts (like I am right now), linkedIn articles, ChemRxiv or bioRxiv preprints etc. It’s a little bit a scientific wild-west happening right now on a global scale.
Discngine dedicates workforce for Covid19
Given the scale of current events and also the fact that we have means to collaborate on some ongoing efforts we decided to get involved. We intend to provide our insights / viewpoints and give a hopefully complementary perspective of what is currently worked on and visible all over the web.
Why you should follow / join efforts during the next weeks?
Current efforts to repurpose existing drugs focus on 3 main targets according to what we’ve seen so far. Efforts in structure-based drug discovery are mainly focused on the main protease right now, some on the Spike protein - ACE2 interaction as well. Clinical trials are run right now on several anti-virals that might have shown effect or not (I won’t enter into the debate about the relevance of hydroxychloroquine tests in France). These are targeted against other intracellular targets.
At Discngine we decided to start a larger effort on a systematic target identification (and binding site ID) on the whole genome of SARS-CoV-2. We intend to propose alternative modes of action than currently pursued. During the next weeks we will systematically analyse each protein encoded by the viral genome, the complexes they form and their biological role. We will hypothesise which type of molecule would allow to alter this biological role (small molecule, peptides, antibodies etc).
All potential targets will be prioritised and further pursued in hit ID stages for drug repurposing, but also for novel hit ID stages. At each step during the process we will communicate our findings here (because it’s the easiest and fastest for us), but we will also summarise findings at intermediate stages in the scientific literature (going through a peer reviewing process). Thus, if you want to be updated immediately on new findings, please follow us here (RSS feed of the blog) or on LinkedIn or Twitter for instance. We are very happy to take comments and suggestions openly and address them.
We need everybody on board!
During the next days and weeks we will come up with suggestions of various modes of actions, targets and binding sites. We won’t be able to follow up on each and everyone ourselves, so we need help from everyone who has good expertise in state of the art molecular modelling & virtual screening techniques. We are already happy to see contributions by Davide Sabbadin, Alessandro Deplano & Alberto Cuzzolin on https://covid.postera.ai (open call for newly designed protease inhibitors) and look forward to see them in 3D very soon (effort on the main protease). They’ll be joined by a very well known pharma in structure-based drug design efforts very shortly. You can already get a quick overview in 3decision of all main protease structures that have been published (X-ray crystallography).
We are very happy to receive also support from several people from the Novartis Institute for Biomedical Research for the upcoming tasks.
Please make sure to follow our efforts
Other useful links to keep you updated?
Summary of molecular modelling efforts: http://www.hecbiosim.ac.uk/covid-19
Christopher Stouthan’s blog: https://cdsouthan.blogspot.com/2020/02/opening-2019-ncov-hamburger.html
Zoé Cournia’s blog: https://lifeischemistry.com/2020/03/27/structure-based-drug-design-updates-for-sars-cov-2/ (very nice timeline on what is released when etc)
Covid Resources collected by Suneel Kumar: http://sbvs.me/covid-resources-for-modellers-medicinal-chemists-ml-scientists/ (info on funding rounds as well)
Fernando Bazan: https://www.linkedin.com/in/j-fernando-bazan-9481a44/ publishes very nice info on linkedIn