Computational simulations on the binding and reactivity of a nitrile inhibitor of the SARS-CoV-2 main protease.
Chem Commun (Camb)
; 57(72): 9096-9099, 2021 Sep 09.
Article
in English
| MEDLINE | ID: covidwho-1373453
ABSTRACT
We present a detailed computational analysis of the binding mode and reactivity of the novel oral inhibitor PF-07321332 developed against the SARS-CoV-2 3CL protease. Alchemical free energy calculations suggest that positions P3 and P4 could be susceptible to improvement in order to get a larger binding strength. QM/MM simulations unveil the reaction mechanism for covalent inhibition, showing that the nitrile warhead facilitates the recruitment of a water molecule for the proton transfer step.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Protease Inhibitors
/
Molecular Dynamics Simulation
/
Coronavirus 3C Proteases
/
SARS-CoV-2
/
Nitriles
Limits:
Humans
Language:
English
Journal:
Chem Commun (Camb)
Journal subject:
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
D1cc03953a
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