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SARS-CoV-2: call for compound predictions against protease

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SARS-CoV-2: call for compound predictions against protease

There is a recently set up call for compound suggests that may be active against the protease SARS-CoV-2, the etiological agent of COVID-19.

Diamond lightsource XChem team did a fragment screen against it and released last week with many hits, which are starting points for designing the next round of compounds.

The target is the protease, here is an interactive description of the protein I made. The model of the wild type peptide substrate (pre-reaction) was made by combining two chains from two crystal structures and energy miniming in Rosetta Relax —it is already aligned against XChem targets.

The crystallised peptide analogue from Yang 2005 is too big, not very drug like and binds with micromolar affinity. Hence the XChem effort.

As the enzyme has a cysteine nucleophile for its activity, the candidate drugs are likely to be a Michael acceptor (ketamide, beta-halo ketone etc.). Most docking programs cannot handle covalently bound compounds. But not Rosetta/pyrosetta!

So if anyone wants to help out, this the chance.


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Sun, 2020-03-22 05:29