Ritonavir's use in blocking the metabolism of other drugs is well known. However, its large effect of 'stuffing the waste basket until full' of CYP 3A4 (and other CYP liver enzymes) so that that a molecule can not be cleared by the liver has the disadvantage of blocking a variety of normal liver functions and of other drugs/small molecules. This a reason that the drug Paxlovid is FDA approved only for high risk groups, i.e., those individuals with predisposition to severe Covid-19, who can accept the risk of Ritonavir. This disadvantage could be eliminated or alleviated by finding other potential small molecule candidates that don't require Ritonavir or other drugs to inhibit ordinary bodily function. This can be accomplished by finding molecules with higher non-covalent interaction with the Mpro cavity and less to the CYP 3A4 enzyme, whether covalent or non-covalent. Comparison of modeled Nirmaltrevir with the 2.0 Angstrom x-ray structure 7SI9 is made. There is good agreement spatially with the highest binding mode, both when non-covalent and covalently bound. In general, the physical pre-covalent binding orientation of a ligand is important to facilitate the chemical covalent reaction. The ligand-cavity hydrogen bonding is examined and it agrees with 2 x-ray covalently bound structures (7SI9, and including those of 7RFR, 7RFS, 7RFU, 7RFW) due to the distributions and specificity of highly scoring epitopes. There are differences between the non-covalent and covalent binding, especially in the hydrogen bonding, and these are pointed out.