Do the potent inhibitors vis SARS-CoV-2 Nsp3-Mac1 are potent as well vis CHICKV-Nsp3-MD

[HadiaAmahli]

ASAP-0015381 is One of the ASAP potent inhibitors vis SARS-CoV-2-Nsp3-MD (PDB reference code: 7H1F) which showed promising activity with IC50= 0.333 µM. The following figure has been taken from our collaborator -DLS team slide demonstrated in the target meeting (3rd June 2024) @jasminaschenbrenner and @DarenFearon.

In our project, we are interested to know if this compound will have the same potency vis CHIKV-Nsp3-MD as well, that's why our protein scientist at UCL: #Wenjie Chen tried to find how similar both targets SARS-CoV-2-Nsp3-MD (PDB reference code: 7H1F) and CHIKV-Nsp3-MD are.

Wenjie Chen demonstrated that the crystal structure of SARS-CoV-2 Nsp3-MD in complex with ASAP-0015381 ( is superposed with CHIKV Nsp3) and he used one of the fragments that offered from XChem.

The following figure shows that the two protein structures overall are very similar, with residues close to the ligands that are different between the two shown. The CHIKV Nsp3 fragment does not occupy the same place as of ASAP-0015381, but close to it, with the closest atoms being 2.3A apart.

[jasminaschenbrenner]

The paper about the tool compounds is still being written but you can reference the ASAP website as well : https://asapdiscovery.org/ The figure in the top is the toolbox compound bound to CHIKV nsP3 macrodomain which isn't clear from the presentation. It is always good to reference the PDB codes as well that were used, e.g. 7H1F for the SARS-CoV-2 nsp3 macrodomain (:

[mattodd]

Welcome to the party @jasminaschenbrenner

[jasminaschenbrenner]

@mattodd Thank you for having me!

[HadiaAmahli]

@jasminaschenbrenner Thank you Jasmin, I think this is a good idea to refer the PDB codes. Feel free to edit wherever it's necessary.