Computational molecular modeling of Paxlovid binding

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


Computational binding modeling of the drug Paxlovid to the 3CL-protease of SARS-Cov-2 is presented. Paxlovid contains 2 molecule ingredients: Nirmatrelvir and Ritonavir. This is a detailed distributional analysis using docking of both small molecules, to the target protease and to the CYP 3A4 liver enzyme. The atomic score interactions are quantified both in the non-covalent binding and in the reversible covalently bound Nirmatrelvir. Conformational analysis is performed for both of the small molecules in binding to the proteins and without using molecular dynamics. The computational binding is used in good comparisons to x-ray determined structures. The total free energy calculations are presented in terms of docking scores and translated to energy at room temperature.


protein-ligand interactions
docking software
small molecule inhibitors
high performance computing
drug design


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