Abstract：
Several viruses hijack various forms of endocytosis in order to infect host cells. Here, we report the discovery of a molecule with antiviral properties that we named virapinib, which limits viral entry by macropinocytosis. The identification of virapinib derives from a chemical screen using high-throughput microscopy, where we identified chemical entities capable of preventing infection with a pseudotype virus expressing the spike (S) protein from SARS-CoV-2. Subsequent experiments confirmed the capacity of virapinib to inhibit infection by SARS-CoV-2, as well as by additional viruses, such as mpox virus and TBEV. Mechanistic analyses revealed that the compound inhibited macropinocytosis, limiting this entry route for the viruses. Importantly, virapinib has no significant toxicity to host cells. In summary, we present the discovery of a molecule that inhibits macropinocytosis, thereby limiting the infectivity of viruses that use this entry route such as SARS-CoV2.
摘要：
几种病毒劫持各种形式的内吞作用以感染宿主细胞。这里,我们报告发现了一种具有抗病毒特性的分子，我们将其命名为韦拉替尼，这限制了巨细胞胞吞作用的病毒进入。韦拉替尼的鉴定来自使用高通量显微镜的化学筛选，其中我们鉴定了能够防止表达SARS-CoV-2的刺突（S）蛋白的假型病毒感染的化学实体。随后的实验证实了韦拉替尼抑制SARS-CoV-2以及其他病毒感染的能力，如猴痘病毒和TBEV。机制分析显示该化合物抑制巨细胞增多症，限制病毒的此进入路径。重要的是,韦拉替尼对宿主细胞无明显毒性。总之,我们发现了一种抑制巨噬细胞增多的分子，从而限制了使用这种进入途径的病毒如SARS-CoV2的感染性。
