K777 是一种有效的，口服活性且不可逆的半胱氨酸蛋白酶 (cysteine protease) 抑制剂，也是一种有效的 CYP3A4 抑制剂，IC50 为 60 nM，是一种选择性的 CCR4 拮抗剂，具有强的趋化性抑制作用。K777 不可逆地抑制锥虫（克鲁斯锥虫的主要半胱氨酸蛋白酶）和组织蛋白酶 B 和 L。K777 是一种广谱抗病毒药物，通过靶向组织蛋白酶介导的细胞进入。K777 抑制 SARS-CoV 和 EBOV 病毒的进入，IC50 值分别为 0.68 nM 和 0.87 nM。
K777 (K11777) can inhibit entry driven by other viral envelope proteins, HIV-based pseudotypes bearing spikes from coronaviruses (SARS-CoV, HCoV-229E, NL63, MERS-CoV) or glycoproteins from filoviruses (EBOV, SUDV, TAFV, RESTV, BEBOV and MARV) are examined. K777 inhibits SARS-CoV, HCoV-229E, NL63, MERS-CoV, EBOV, SUDV, TAFV, RESTV, BEBOV, MARV and Nipah pseudovirus entry with IC
50
values of 0.68 nM, 1.48 nM, 6.78 nM, 46.12 nM, 0.87 nM, 1.14 nM, 2.26 nM, 3.37 nM, 5.91 nM, 1.9 nM and 0.42 nM, respectively. In contrast, 100 nM K777 does not inhibit infection mediated by envelope glycoproteins from an alphavirus (CHIKV), a rhabdovirus (VSV), a flavivirus (HCV), the retroviruses MLV-A and XMRV or two arenaviruses, Lassa and Junin virus.
Whether K777 displays antiviral activity in TMPRSS2 expressing cells are assessed. For this, the incubated target cells with Camostat, K777, or a combination of K777 and Camostat and then infected with pseudoviruses bearing 229E-S. K777 alone demonstrates up to ~ 70% inhibition of 229E-S-mediated transduction. Simultaneous treatment with Camostat and K777 increases inhibition to ~ 90%. Similar inhibition patterns are obtained using the human intestinal epithelial cell line Caco-2, which express endogenous TMPRSS2 and cathepsins.
K777 inhibits both CCL17 binding and CCL17-induced chemotaxis in Hut78 cells (IC
50
of 57 and 8.9 nM, respectively). The K777-mediated inhibition of chemotaxis is potent even in the presence of a 10-fold higher concentration of CCL17. K777 induces CCR4 internalization, with a ∼50% reduction of cell surface CCR4. K777 does not inhibit CXCR4-induced chemotaxis or internalization and did not bring about Ca
2+
mobilization by itself.