lar structure fragments), the topomer strategy is used to examine and come across the molecular fragments with similarity. The Topomer Distance (TOPDIST) along with the Cathepsin K Formulation contribution value of substituents are integrated and the established Topomer CoMFA model scores these fragments and performs virtual screening on the cleaved fragments toJ.-B. TONG, X. ZHANG, D. LUO et al.Chinese Journal of Analytical Chemistry 49 (2021) 63Fig. 4. (a): Prototype molecular generation diagram (Green region represents prototype molecule). (b): Compound 33 interacts using the active web site of protein 7JYC.get R1 , R2 and R3 substituents with larger contribution worth. Then, SARS-CoV-2 inhibitor tiny molecules with far better activity are obtained by splicing style. 2.7. Molecular docking study Molecular docking is among the most generally utilised methods to study the mutual recognition procedure of geometric matching and power matching in drug design and style. The principle of molecular docking would be the “lock and key model” [33]. The lock is a macromolecular receptor with different structures, and the key is usually a smaller molecule ligand using a certain structure. When the macromolecular receptor plus the smaller molecule ligand are complementary and matched in geometry, the electrostatic interactions, hydrogen bond interactions and hydrophobic interactions will occur. Then, in the process of binding, the conformation of your tiny molecule ligand and its surrounding amino acid conformation gradually adjust, adapt to each other and induce fit. In order to exert its inhibitory activity against SARS-CoV-2, cyclic sulfonamide compounds want to have certain affinity with SARS-CoV2 enzyme protein. Following the two are sufficiently close to one another, they will combine with each other and interact with one another by means of appropriate conformational adjustment, lastly forming a steady complex conformation [34]. Surflex-Dock requires polarity effect, hydrophobic impact and hydrogen bond impact into account to score the interaction among ligand and receptor, and the Total score is the dissociation constant (representing docking activity). We use SYBYL-X 2.0 (SurflexDock technique) and Discovery Studio Visualization tool 2017 to study the molecular docking with the least active compound(2, three, 7, eight, 25, 26, 27, 29) along with the most active compound 33 together with the 7JYC protein around the data set reported inside the ALK3 manufacturer earlier experimental research to further analyze and confirm the molecular structure of cyclic sulfonamide compounds [35]; and by means of the comparison of your two techniques, the cause why compound 33 includes a larger inhibitory activity against SARS-CoV-2 is explained. Lastly, the four newly developed inhibitor molecules are docked to understand the antiviral mechanism in the created compound. The three-dimensional crystal structure of protease (7JYC) comes from the PDB database (http://rcsb.org/). Before molecular docking, the protein receptor molecules are pretreated, the needed smaller molecule ligands are extracted from the macromolecular complexes, and the own ligands, metal ions, water molecules, as well as other residues and terminal residues of protein are removed. Polar hydrogen and point charges are added to expose the binding pocket (represented by the prototype molecule) [36]. The binding pocket is filled with hydrogen bond donors, hydrogen bond acceptors and hydrophobic web site molecular probes. The interaction mode from the processed prototype smaller molecule and protein macromolecule is shown in Fig. 4(a). The crystal structur