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.

中文翻译：

---

发现具有抗病毒活性的新型巨胞饮抑制剂


几种病毒劫持各种形式的内吞作用以感染宿主细胞。在这里，我们报告了一种具有抗病毒特性的分子的发现，我们将其命名为维拉匹尼，它通过巨胞饮作用限制病毒进入。维拉匹尼的鉴定源自使用高通量显微镜的化学筛选，其中我们鉴定了能够预防表达 SARS-CoV-2 刺突 (S) 蛋白的假型病毒感染的化学实体。随后的实验证实了维拉匹尼抑制 SARS-CoV-2 以及其他病毒（例如mpox病毒和TBEV）感染的能力。机理分析表明，该化合物抑制巨胞饮作用，限制病毒的进入途径。重要的是，维拉匹尼对宿主细胞没有明显的毒性。总之，我们发现了一种抑制巨胞饮作用的分子，从而限制了使用这种进入途径的病毒（例如 SARS-CoV2）的感染性。