CACHE Challenge #2 Round 1 Experimental Validation Data

CACHE#2 compounds are tested experimentally at the Structural Genomics Consortium, University of Toronto, with contributions from Cheryl Arrowsmith, Albina Bolotokova, Peter J. Brown, Irene Chau, Kristina Edfeldt, Pegah Ghiabi , Elisa Gibson, Oleksandra Herasymenko, Rachel Harding, Zarah Hejazi, Scott Houliston, Ashley Hutchinson, Carla Kharadjian, Helen Li, Peter Loppnau, Sumera Perveen, Matthieu Schapira, Almagul Seitova and Madhushika Silva. Structural biology is conducted at the Centre for Medicines Discovery, University of Oxford, with contributions from Joseph Newman.

Here are the results from the experimental validation of compounds from the first round of selections for CACHE challenge #2.

THE CHALLENGE

CACHE participants were asked to use their computational methods to find hits for the RNA-binding site of the SARS-CoV-2 helicase NSP13. See details.
After a double-blind peer review where each applicant reviewed 5 applications, 23 participants joined the challenge, representing a diverse array of physics-based and AI computational methods.
Participants collectively selected 1957 compounds (no more than 100 compounds per participant) that we ordered and received from Enamine.
All experimental data except the structure of the compounds are provided here and explained here.
The structure of the compounds will be provided at the end of the second (hit-expansion) round of the challenge.
A summary is available here and associated computational methods are available here.

EXPERIMENTAL VALIDATION

Compounds were screened at 50 µM against the SARS-CoV-2 helicase NSP13 in an SPR binding assay.
Hit candidates were tested in a dose-response experiment.
Forty-six compounds selected by 18 participants are advancing to the hit-expansion phase (Round 2) of this CACHE challenge, where participants can select up to 50 follow-up compounds for experimental characterization.

Download an excel table of the results here and associated information file here.