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丝氨酸蛋白酶和宿主细胞受体在新冠病毒蛋白水解激活、进入过程中的作用及其当前治疗选择

Role of Serine Proteases and Host Cell Receptors Involved in Proteolytic Activation, Entry of SARS-CoV-2 and Its Current Therapeutic Options.

作者信息

Dessie Gashaw, Malik Tabarak

机构信息

Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.

出版信息

Infect Drug Resist. 2021 May 24;14:1883-1892. doi: 10.2147/IDR.S308176. eCollection 2021.

Abstract

The current global pandemic of a novel severe acute respiratory syndrome coronavirus-2 continues with its public health disaster beginning from late December 2019 in Wuhan, Hubei province, China. The scientific community has tried to fight against this novel coronavirus through vaccine development and designing different candidate drugs. However, there is no well-defined therapy to prevent 2019-nCov infection, thus complete prevention of the virus remains difficult. Therefore, it is a critical factor for death of millions worldwide. Many clinical trials and insights are ongoing in the struggle with this pandemic of SARS-CoV-2. SARS-CoV-2 entry into the host cell requires host cell angiotensin-converting enzyme-2 (ACE2) and glucose regulated protein 78 (GRP78). On the other hand, proteolytic activation of the viral spike protein (S protein) needs the host cell serine proteases, including transmembrane serine protease 2 (TMPRSS2), cathepsins, trypsin and furin. This review focuses on the protein involved in the mechanism of entry, and proteolytic activation. In addition, it looks at current therapeutic options for SARS-CoV-2.

摘要

当前,新型严重急性呼吸综合征冠状病毒2引发的全球大流行仍在持续,自2019年12月底在中国湖北省武汉市爆发以来,已演变成一场公共卫生灾难。科学界一直在努力通过研发疫苗和设计不同的候选药物来对抗这种新型冠状病毒。然而,目前尚无明确的疗法来预防2019新型冠状病毒感染,因此完全预防该病毒仍然困难重重。所以,这是导致全球数百万人死亡的一个关键因素。目前,针对严重急性呼吸综合征冠状病毒2大流行的斗争中,许多临床试验和研究正在进行。严重急性呼吸综合征冠状病毒2进入宿主细胞需要宿主细胞血管紧张素转换酶2(ACE2)和葡萄糖调节蛋白78(GRP78)。另一方面,病毒刺突蛋白(S蛋白)的蛋白水解激活需要宿主细胞丝氨酸蛋白酶,包括跨膜丝氨酸蛋白酶2(TMPRSS2)、组织蛋白酶、胰蛋白酶和弗林蛋白酶。本综述重点关注参与病毒进入机制和蛋白水解激活过程的蛋白质。此外,还探讨了目前针对严重急性呼吸综合征冠状病毒2的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f34/8163626/194c40272ae2/IDR-14-1883-g0001.jpg

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