One of the best drug targets among coronaviruses is the main protease (Mpro), this enzyme is essential for processing the polyproteins that are translated from the viral RNA and the recognition sequence at most sites is Leu-Gln↓(Ser,Ala,Gly) and since no human enzymes have similar specificity inhibitors should be very specific. Mpro is a papain-like protease cysteine protease

I've previously described the fragment hits from a fragment screen against crystals of the main protease (MPro) of SARS-CoV-2, the virus that causes COVID-19. Full details of the screening effort are described here https://www.diamond.ac.uk/covid-19/for-scientists/Main-protease-structure-and-XChem/Downloads.html

The results of the first round of biological results from project moonshot are in. You can browse the data here https://postera.ai/covid/activity_data.

Most of the most active compounds are chloroketones or acrylamides, presumably covalent inhibitors, and they all show selectivity over Trypsin (IC50 >99 uM).

There are a few structures that look more like competitive inhibitors shown below

A number of these structures now have crystal structures available.

A sdf file containing these non-covalent structures is here

Fantastic work by all involved.