Open source competition finds potential corona drugs

The CACHE (Critical Assessment of Computational Hit-Finding Experiments) challenge has sparked further new research – this time identifying seven promising molecules that could become pan-coronavirus drugs.

22 teams were faced with the challenge of finding a molecule that can bind to the RNA binding site of the NSP13 helicase, a SARS-CoV-2 replication protein that is conserved across several coronavirus types.

These molecules, or “hits,” were identified by teams using various in silico drug discovery platforms. These hits were then experimentally tested at the Structural Genomics Consortium at the University of Toronto to see if they could actually bind to the identified target. The molecules and the data behind them are available for anyone to develop freely.

According to Ryan Merkley, CEO of Conscience, the organizer of the competition, these open science competitions provide drug research groups with the opportunity to test their technology against others.

“The pharmaceutical industry traditionally works in its silos,” he says. “There are not many areas where you can directly compare performance.”

The winning team, determined based on the number and strength of the molecules identified, was led by Karina dos Santos Machado, who hails from the Universidade Federal do Rio Grande and the Universidade Federal de Pelotas – both universities in Brazil. The team used both open-source and in-house developed AI methods to identify their molecules.

Another team from Vanderbilt University, led by Rocco Moretti, scored highly, using Drugit, a design mode of the citizen science game Foldit. Players were given a series of puzzles to design a molecule, and over 150 players submitted 7598 possible compounds. After narrowing the number down to 111 compounds to order and test, CACHE selected one molecule as a hit.

“I think there's a lot of room for human intuition in discovering these new molecules,” says Moretti. “There's a lot we don't necessarily understand about the interactions between proteins and small molecules. And with that human knowledge of what might fit in the bag, what the hydrogen bonding pattern should look like, I think citizen scientists can contribute.”