Unidad de Investigación Médica en Inmunología, Unidad Medica de Alta Especialidad, Hospital de Pediatría, Centro Médico Nacional "Siglo XXI", Instituto Mexicano del Seguro Social, Cuauhtémoc 330, Mexico Ctiy 06720, Mexico.
Sección de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Mexico Ctiy 14080, Mexico.
Viruses. 2021 Jan 17;13(1):121. doi: 10.3390/v13010121.
Quinacrine (Qx), a molecule used as an antimalarial, has shown anticancer, antiprion, and antiviral activity. The most relevant antiviral activities of Qx are related to its ability to raise pH in acidic organelles, diminishing viral enzymatic activity for viral cell entry, and its ability to bind to viral DNA and RNA. Moreover, Qx has been used as an immunomodulator in cutaneous lupus erythematosus and various rheumatological diseases, by inhibiting phospholipase A2 modulating the Th1/Th2 response. The aim of this study was to evaluate the potential antiviral effect of Qx against denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Vero E6 cells. The cytotoxicity of Qx in Vero E6 cells was determined by the MTT assay. Afterwards, Vero E6 cells were infected with SARS-CoV-2 at different multiplicities of infections (MOIs) of 0.1 and 0.01 in the presence of Qx (0-30 µM) to determinate the half maximal effective concentration (EC). After 48 h, the effect of Qx against SARS-CoV-2 was assessed by viral cytotoxicity and viral copy numbers, the last were determined by digital real-time RT-PCR (ddRT-PCR). Additionally, electron and confocal microscopy of Vero E6 cells infected and treated with Qx was studied. Our data show that Qx reduces SARS-CoV-2 virus replication and virus cytotoxicity, apparently by inhibition of viral ensemble, as observed by ultrastructural images, suggesting that Qx could be a potential drug for further clinical studies against coronavirus disease 2019 (COVID-19) infection.
吖啶（Qx）是一种用作抗疟药物的分子，具有抗癌、抗朊病毒和抗病毒活性。Qx 最相关的抗病毒活性与其在酸性细胞器中升高 pH 值的能力有关，降低病毒进入细胞的酶活性，以及与病毒 DNA 和 RNA 结合的能力。此外，Qx 已被用作皮肤红斑狼疮和各种风湿病的免疫调节剂，通过抑制磷脂酶 A2 调节 Th1/Th2 反应。本研究旨在评估 Qx 对 Vero E6 细胞中命名为严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的潜在抗病毒作用。通过 MTT 测定法测定 Qx 在 Vero E6 细胞中的细胞毒性。然后，用 SARS-CoV-2 在不同的感染复数（MOI）0.1 和 0.01 在 Qx（0-30µM）存在下感染 Vero E6 细胞，以确定半最大有效浓度（EC）。48 小时后，通过病毒细胞毒性和病毒拷贝数评估 Qx 对 SARS-CoV-2 的作用，最后通过数字实时 RT-PCR（ddRT-PCR）确定。此外，还研究了感染和用 Qx 处理的 Vero E6 细胞的电子和共聚焦显微镜。我们的数据表明，Qx 减少了 SARS-CoV-2 病毒的复制和病毒细胞毒性，显然是通过抑制病毒集合来实现的，如超微结构图像所示，这表明 Qx 可能是一种针对 2019 年冠状病毒病（COVID-19）感染的潜在临床研究药物。
