COVID-19 在 2020 年引起全球大流行，是由 SARS-冠狀病毒 2 (SARS-CoV-2) 引起的疾病。該病毒具有高度傳染性，具有多種臨床症狀，如呼吸道症狀、發熱、腹瀉、嗅覺和味覺異常。迄今為止，尚無抑制宿主細胞內病毒感染或擴增的特異性藥物。疫苗可有效防止病毒感染或傳播，但冠狀病毒突變頻率高，必須對原有疫苗進行改進，以提高保護效果。 3C 樣蛋白酶 (3CLpro) 是冠狀病毒中發現的主要蛋白酶，它幾乎沒有發生突變，對於 SARS-CoV-2 的複製至關重要。 3CLpro 與宿主細胞之間的相互作用鮮為人知。本研究首先使用慢病毒在A549細胞中表達3CLpro，發現Oct-1蛋白的表達顯著降低。已經提到 Oct-1 的缺失會導致細胞死亡，我們證明 3CLpro 的表達足以抑制細胞生長並誘導細胞死亡，並且相關的信號分子，如Erk、Akt、p53 和 LC3-II 也被失調。最後，我們使用銀杏提取物來恢復 3CLpro 誘導的生長抑制細胞死亡，這意味著銀杏提取物可能通過 3CLpro 的靶點對 COVID-19 具有治療益處。

COVID-19, which causes a global pandemic in 2020, is a disease caused by SARS-coronavirus 2 (SARS-CoV-2). The virus is highly infectious and has multiple clinical symptoms, such as respiratory symptoms, fever, diarrhea, and abnormal smell and taste. To date, there are no specific drugs to inhibit virus infection or amplification within host cells. Vaccines effectively prevent viral infection or spreading. Because coronavirus has high mutation frequency, the original vaccine usually needs to be improved for better protection. 3C-like protease (3CLpro) is the main protease found in coronaviruses. It is barely mutated and essential for the replication of SARS-CoV-2. The interaction between 3CLpro and host cell remains largely unknown. In this study, we first used lentiviral vectors to express 3CLpro in A549 cells and found that the expression of Oct-1 protein is significantly decreased. Loss of Oct-1 has been shown to cause cell death. We demonstrate that the expression of 3CLpro can inhibit cell growth and induce cell death, as well as dysregulate the related signaling molecules, such as Erk, Akt, p53, and LC3-II. Finally, we show that the Ginkgo extract can restore 3CLpro-induced cell death, suggesting that the Ginkgo extract may have the therapeutic benefit for COVID-19 via targeting 3CLpro.

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