维生素 C 促进 ACE2 降解并防止 SARS-CoV-2 感染。
Vitamin C promotes ACE2 degradation and protects against SARS-CoV-2 infection.
机构信息
International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China.
出版信息
EMBO Rep. 2023 Apr 5;24(4):e56374. doi: 10.15252/embr.202256374. Epub 2023 Mar 6.
ACE2 is a major receptor for cellular entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2 binding, strategies to flexibly and sufficiently reduce ACE2 levels for the prevention of SARS-CoV-2 infection have not been explored. Here, we reveal vitamin C (VitC) administration as a potent strategy to prevent SARS-CoV-2 infection. VitC reduces ACE2 protein levels in a dose-dependent manner, while even a partial reduction in ACE2 levels can greatly inhibit SARS-CoV-2 infection. Further studies reveal that USP50 is a crucial regulator of ACE2 levels. VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination of ACE2 at Lys788 and subsequent degradation of ACE2 without affecting its transcriptional expression. Importantly, VitC administration reduces host ACE2 levels and greatly blocks SARS-CoV-2 infection in mice. This study reveals that ACE2 protein levels are down-regulated by an essential nutrient, VitC, thereby enhancing protection against infection of SARS-CoV-2 and its variants.
ACE2 是 SARS-CoV-2 进入细胞的主要受体。尽管在针对 ACE2 以抑制 SARS-CoV-2 结合方面取得了进展，但尚未探索出灵活且充分降低 ACE2 水平以预防 SARS-CoV-2 感染的策略。在这里，我们揭示了维生素 C（VitC）的应用是预防 SARS-CoV-2 感染的有效策略。VitC 呈剂量依赖性降低 ACE2 蛋白水平，而 ACE2 水平的部分降低即可大大抑制 SARS-CoV-2 感染。进一步的研究表明，USP50 是 ACE2 水平的重要调节因子。VitC 阻断 USP50-ACE2 相互作用，从而促进 ACE2 在 Lys788 处发生 K48 连接的多泛素化，并随后降解 ACE2，而不影响其转录表达。重要的是，VitC 的给予可降低宿主 ACE2 水平，并大大阻断 SARS-CoV-2 在小鼠中的感染。本研究揭示 ACE2 蛋白水平受必需营养素 VitC 的下调，从而增强了对 SARS-CoV-2 及其变体感染的保护作用。
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