The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Cystatins are natural inhibitors of papain-like (family C1) and legumain-related (family C13) cysteine peptidases. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. As a member of type 2 cystatin, cystatin D is a single-domain protein and also has cysteine residues that form disulfide bridges. The functions of Cystatin D are largely unknown. However, Cystatin D has been shown to inhibit coronavirus replication at its physiological concentration (0.12_x005f