POLYPEPTIDE-COUPLED SMALL MOLECULE COMPOUND AND ANTIVIRAL APPLICATION THEREOF

A polypeptide-coupled small molecule compound and its antiviral applications are provided. The polypeptide-coupled small molecule compound is obtained by linking a polypeptide with a sequence X′nLXGG and a small molecule compound capable of inhibiting activity of papain-like protease (PLpro) of coronavirus through a chemical bond. The polypeptide with the sequence X′nLXGG is a polypeptide with a sequence LXGG at its carboxyl terminal, X and X′ are independently any amino acid, and n is an integer between 1-50. The structure of the small molecule compound capable of inhibiting the activity of PLpro contains an amino group or a hydroxyl group. The polypeptide-coupled small molecule compound can inhibit the PLpro of SARS-CoV-2 in a targeted manner, thereby inhibiting the polyprotein cleavage of coronavirus in the host, and achieving the purpose of inhibiting the replication of coronavirus in the host. It has the advantages of synergistic inhibition, low cytotoxicity and favorable solubility.