May 11, 2020

Insilico Medicine continues publishing its results on generating novel potential chemotypes targeting SARS-CoV-2 main protease (Mpro), one of the most important SARS-CoV-2 protein targets. In our previous work we used the first Mpro crystal structure to become available, 6LU7. On February 4, 2020 Insilico Medicine released the first potential novel protease inhibitors designed using a de novo , AI-driven generative chemistry approach. Nearly 100 X-ray structures of Mpro co-crystallized both with covalent and non-covalent ligands have been published since then. Here we utilize the recently published 6W63 crystal structure of Mpro complexed with a non-covalent inhibitor and combined two approaches used in our previous study: ligand-based and crystal structure–based. We published 10 representative structures for potential development in SDF format along with 3D representation in PDB format and welcome medicinal chemists for broad discussion and generated output analysis. The preprint is available in the COVID-19 section on the ResearchGate preprint server. Selected ligand-protein complexes were additionally assessed during a VR session kindly carried out by the Nanome team and you can watch it below.
The paper is available for comments on ResearchGate and ChemRxiv

February 4, 2020

Insilico Medicine announces that it will publish structures of small molecules targeting the key protein SARS-CoV-2 3C-like protease. It will synthesize and test up to 100 molecules using its own resources and the resources generously offered by its closest partners, to contribute to the global effort. The rest of the structures are published on the company website with the annotation submitted to the pre-print server. By making these structures available to the general public, Insilico hopes those who are interested in finding a potential treatment for this viral infection could synthesize and test these molecules.

One of the bottlenecks in AI-powered drug discovery is the ability to synthesize and test the molecules quickly. Advanced generative chemistry approaches allow for many diverse molecular structures to be designed with a variety of properties as generation conditions. However, synthesis and validation may take some time and could require substantial resources. Therefore, Insilico Medicine selected up to 100 molecules to be synthesized and tested, with the rest of the generated structures deposited on the website.

For synthesis and screening Insilico joined forces with many functions of the largest international open research platform, and the company will make its staff and resources available to support drug discovery process to contribute to the global fight against this new health threat.

"During this difficult time, every promising approach must be used to expedite the drug discovery efforts against SARS-CoV-2, including utilizing the generative chemistry part of our end-to-end drug discovery pipeline. We encourage medicinal chemists to evaluate the generated molecules, provide their feedback and consider them for synthesis. Our team will also synthesize and test several of the generated compounds" said Alex Zhavoronkov, PhD, CEO of Insilico Medicine.
The 6 molecules in the paper are representative molecules from the first batch of generation.
Please download the SDF file with the most recent batch.
The paper and the molecules are available for comments
on ResearchGate and ChemRxiv