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使用天然半胱氨酸蛋白酶抑制剂来限制新冠病毒与人类呼吸道细胞的融合。

Use of natural cysteine protease inhibitors in limiting SARS-Co-2 fusion into human respiratory cells.

作者信息

Siewiński Maciej, Bażanów Barbara, Orzechowska Beata, Gołąb Krzysztof, Gburek Jakub, Matkowski Adam, Rapak Andrzej, Janocha Anna, Krata Lechosław, Dobrzyński Maciej, Kilar Ewa

机构信息

Wroclaw Medical University, TherapyRaft Comp., Wroclaw, Poland.

Wrocław University of Environmental and Life Sciences, Faculty of Veterinary Medicine, Department of Pathology, C.K.Norwida 31, 50-375 Wrocław, Poland.

出版信息

Med Hypotheses. 2022 Nov;168:110965. doi: 10.1016/j.mehy.2022.110965. Epub 2022 Oct 26.

Abstract

Specific antibodies that humans acquire as a result of disease or after vaccination are needed to effectively suppress infection with a specific variant of SARS CoV-2 virus. The S protein of the D614G variant of coronavirus is used as an antigen in known vaccines to date. It is known that COVID-19 disease resulting from infection with this coronavirus can often be very dangerous to the health and lives of patients. In contrast, vaccines produce antibodies against an older version of the protein S-D614G (January 2020) and therefore have difficulty recognizing new variants of the virus. In our project we propose to obtain specific and precise antibodies by means of so-called controlled infection against specific infectious variants of the SARS-CoV-2 virus "here and now". Currently, several variants of this pathogen have already emerged that threaten the health and lives of patients. We propose to reduce this threat by partially, but not completely, blocking the fusion mechanism of the SARS-CoV-2 virus into human respiratory cells. According to our plan, this can be achieved by inhibiting cathepsin L activity in respiratory cells, after introducing natural and non-toxic cysteine protease inhibitors into this area. We obtain these inhibitors by our own method from natural, "human body friendly" natural resources. We hypothesize that blocking cathepsin L will reduce the number of infecting viruses in cells to such an extent that COVID-19 developing in infected individuals will not threaten their health and life. At the same time, the number of viruses will be sufficient for the body's own immune system to produce precise antibodies against a specific version of this pathogen.

摘要

人类因疾病或接种疫苗后获得的特异性抗体,对于有效抑制感染新冠病毒特定变体至关重要。迄今为止,已知疫苗中使用冠状病毒D614G变体的S蛋白作为抗原。众所周知,感染这种冠状病毒导致的新冠肺炎疾病,往往对患者的健康和生命构成极大威胁。相比之下,疫苗产生的是针对旧版S-D614G蛋白(2020年1月)的抗体,因此难以识别该病毒的新变体。在我们的项目中,我们提议通过所谓的可控感染,针对当下新冠病毒的特定感染变体获取特异性和精准性抗体。目前,这种病原体已经出现了几种变体,威胁着患者的健康和生命。我们提议通过部分但非完全阻断新冠病毒与人类呼吸道细胞的融合机制来降低这种威胁。根据我们的计划,在向该区域引入天然且无毒的半胱氨酸蛋白酶抑制剂后,通过抑制呼吸道细胞中的组织蛋白酶L活性可以实现这一点。我们通过自己的方法从天然的、“对人体友好”的自然资源中获取这些抑制剂。我们假设阻断组织蛋白酶L将把细胞中感染病毒的数量减少到一定程度,使得感染者体内发展的新冠肺炎不会威胁到他们的健康和生命。与此同时,病毒数量将足以让人体自身免疫系统产生针对该病原体特定版本的精准抗体。

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