Cys145 covalent inhibition

Does anyone know how to test in-silico covalent interaction between the Cys145 sulfur and a tiol group of a ligand? Like to establish a disulfide not-reversible Mpro trapping.

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One would need to do covalent docking to see if it fits okay. Then model the transition state or the encounter complex to see if the “hill” is surmountable.

However, the latter is a bit problematic. If you have two thiols, i.e. your ligand’s thiol and the cysteine’s thiol, you need to oxide them. So your ligand would need to be in a disulfide form, or something similar —unless you ignore the problem of getting rid of an electron pair.

If the redox is not an issue and it’s only a few compounds and you have in mind and in SMILES format (these can be found by searching a compound name in pubchem or right click in ChemDraw) I can do it for you.

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