The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the mechanisms of SARS-CoV-2 infection and host responses, which is coupled to the practical experience of clinicians that are treating patients. Because SARS-CoV-2 enters the cell by binding to angiotensin-converting enzyme 2 (ACE2), targeting ACE2 to prevent such binding seems an obvious strategy to combat infection. However, ACE2 performs its functions outside the cell and was found to enter the cell only by angiotensin II type 1 receptor (AT1R)-induced endocytosis, after which ACE2 is destroyed. This means that preventing uptake of ACE2 into the cell by blocking AT1R would be a more logical approach to limit entry of SARS-CoV-2 into the cell. Since ACE2 plays an important protective role in maintaining key biological processes, treatments should not disrupt the functional capacity of ACE2, to counterbalance the negative effects of the infection. Based on known mechanisms and knowledge of the characteristics of SARS-CoV we propose the hypothesis that the immune system facilitates SARS-CoV-2 replication which disrupts immune regulatory mechanisms. The proposed mechanism by which SARS-CoV-2 causes disease immediately suggests a possible treatment, since the AT1R is a key player in this whole process. AT1R antagonists appear to be the ideal candidate for the treatment of SARS-CoV-2 infection. AT1R antagonists counterbalance the negative consequences of angiotesnin II and, in addition, they might even be involved in preventing the cellular uptake of the virus without interfering with ACE2 function. AT1R antagonists are widely available, cheap, and safe. Therefore, we propose to consider using AT1R antagonists in the treatment of SARS-CoV-2.

中文翻译：

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SARS-CoV-2 使用血管紧张素转换酶 2 进入细胞进行复制的机制概述：与肾素-血管紧张素系统相关的可能治疗选择。

SARS-CoV-2 大流行是一场医疗危机，是由于有效对抗该病毒的知识不足而引起的。因此，需要将不同的科学发现策略联系起来，以产生可以尽快提供的合理治疗方法。这依赖于对 SARS-CoV-2 感染机制和宿主反应的扎实理论理解，并与治疗患者的临床医生的实践经验相结合。由于 SARS-CoV-2 通过与血管紧张素转换酶 2 (ACE2) 结合进入细胞，因此靶向 ACE2 来阻止这种结合似乎是对抗感染的明显策略。然而，ACE2 在细胞外发挥其功能，并且被发现仅通过血管紧张素 II 1 型受体 (AT1R) 诱导的内吞作用进入细胞，之后 ACE2 被破坏。这意味着通过阻断 AT1R 来阻止 ACE2 进入细胞将是限制 SARS-CoV-2 进入细胞的更合理的方法。由于 ACE2 在维持关键生物过程中发挥着重要的保护作用，因此治疗不应破坏 ACE2 的功能，以抵消感染的负面影响。基于已知的机制和对 SARS-CoV 特征的了解，我们提出这样的假设：免疫系统促进 SARS-CoV-2 复制，从而破坏免疫调节机制。由于 AT1R 是整个过程中的关键角色，因此提出的 SARS-CoV-2 致病机制立即表明了可能的治疗方法。AT1R 拮抗剂似乎是治疗 SARS-CoV-2 感染的理想候选药物。AT1R 拮抗剂可以抵消血管紧张素 II 的负面影响，此外，它们甚至可能参与阻止细胞摄取病毒，而不干扰 ACE2 功能。AT1R 拮抗剂广泛可用、廉价且安全。因此，我们建议考虑使用 AT1R 拮抗剂治疗 SARS-CoV-2。