Leading the Medicinal Chemistry on the COVID Moonshot: A refelection by Dr Ed Griffen
Back at the start of the COVID-19 pandemic we were invited to join the COVID Moonshot project. It’s a self starting open science academic-industrial collaboration. The foundation was rapid fragment screening at the Diamond facility in Oxford, biochemistry from the Weizmann Institute in Israel, synthetic chemistry machine learning from Postera, massive scale FEP from Memorial Sloan Kettering Cancer Centre and chemistry at Enamine. [https://postera.ai/moonshot]
The remarkable speed of the early hit finding is detailed here [Nature Communications | (2020)11:5047 | https://doi.org/10.1038/s41467-020-18709-w] and the way the team then expanded and configured itself to move from hits to in vivo leads is described here[Nature | (2021) 594, 330-332 | https://doi.org/10.1038/d41586-021-01571-1].
Reflecting on what we have learned…
Now is a good moment to reflect a little on what we’ve learnt, and a small part of the medicinal chemistry is being shared at the 21st RSC / SCI Medicinal Chemistry Symposium this week. Although it only took 300 compounds tested to get to a sub micro-molar enzymatic lead, the process to get compounds that are highly active in cells with acceptable in vivo characteristics has taken another 1800 compounds, but was achieved in just a year. We have a highly experienced medicinal chemistry team and have used many of the leading tools for optimising compounds. Still, solving metabolism issues is a tough task especially as we have been operating with a very limited budget. It’s been an incredible journey so far, and with the prospect of putting multiple compounds into pre-clinical development in sight, as ever, the motivator is putting science in the service of saving lives.