Computational Study of Paxlovid in Ligand GA

10 February 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Ligand GA is used to generate potentially realistic inhibitors of the 3CL protease of the SARS-Cov-2 virus by starting with the Nirmatrelvir molecule and changing it. After post-processing of the molecules using an extensive set of docking parameters, several of the molecules are selected and presented in detail that have good inhibition and metabolic activity, and binding increased to Mpro, while small change occurred in the binding to the liver enzyme CYP 3A4. This is a computational study of realistic potential inhibitors of the SARS-Cov-2 main protease found by using this software, with multiple results of which some are highlighted in particular. Of note is that these molecules may not require a CYP liver enzyme inhibitor such as Ritonavir in practical application.


drug design
machine learning
protein-ligand interactions
high performance computing
genetic algorithms
small molecule inhibitors

Supplementary weblinks


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