Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine.
Department of Respiratory Medicine, Tohoku University Graduate School of Medicine.
Tohoku J Exp Med. 2020 May;251(1):27-30. doi: 10.1620/tjem.251.27.
The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 μg/mL) or nafamostat (0.01-1 μg/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.
新型冠状病毒（SARS-CoV-2）感染患者数量迅速增加，尽管世界卫生组织已宣布其为大流行疾病。然而，目前尚未发现针对 SARS-CoV-2 的有效药物。SARS-CoV-2 被认为与血管紧张素转化酶 2（SARS 冠状病毒的受体）结合。SARS 冠状病毒和引起普通感冒的冠状病毒 229E 通过细胞表面和内体途径利用一种蛋白酶，即 II 型跨膜蛋白酶进行复制。为了研究蛋白酶抑制剂对冠状病毒 229E 复制的影响，我们用卡莫司他或那屈肝素预处理人鼻上皮（HNE）细胞原代培养物，这两种蛋白酶抑制剂均被用于治疗胰腺炎和/或弥散性血管内凝血。然后用冠状病毒 229E 感染 HNE 细胞，并检测细胞气道表面液体中的病毒滴度。卡莫司他（0.1-10 μg/mL）或那屈肝素（0.01-1 μg/mL）预处理可降低冠状病毒 229E 的滴度。此外，在 HNE 细胞的气道表面液体中检测到大量 II 型跨膜蛋白酶蛋白。此外，干扰素已被报道对 SARS 冠状病毒具有抗病毒作用。干扰素对洛匹那韦、利托那韦和法匹拉韦等其他候选药物抑制 SARS-CoV-2 感染的抑制作用的协同作用也进行了研究。这些发现表明，此类蛋白酶抑制剂可能以临床浓度抑制人呼吸道上皮细胞中冠状病毒 229E 的复制。蛋白酶抑制剂、干扰素或这些药物的联合用药可能成为抑制 SARS-CoV-2 复制的候选药物。
