Nirmatrelvir, i.e. PF-07321332, is a small molecule that binds to a particular region of the SARS-Cov-2 main protease, blocking proteolytic cleavage of some of the SARS-Cov-2 polyproteins , hence viral replication at an early stage of infection. It and Ritonavir are the components of Paxlovid, the Pfizer orally ingested therapeutic for treating SARS-Cov-2 post-infection. The x-ray structure of Nirmatrelvir covalently bound to the SARS-Cov-2 3CL protease, aka Mpro, is available at the Protein Data Bank, PDB ID 7SI9 . The molecule is a descendant of an earlier created molecule, PF-00835231 , created during the SARS-Cov-1 outbreak in 2003. In this section the interaction of Nirmatrelvir to SARS-Cov-2 3CL protease is used to demonstrate the docking protocol, in pre-covalent and covalent binding. Noncovalent ligand interaction and orientation of the bound ligand is necessary for the covalent reaction to occur.