Influenza virus infection continues to cause significant, often severe, respiratory illness worldwide. A validated target for the development of anti‐influenza agents is the virus surface protein sialidase. In the current study, we have discovered a highly potent inhibitor of influenza virus sialidase, based on a novel sialosyl sulfonate template. The synthesised 3‐guanidino sialosyl α‐sulfonate, a sulfonozanamivir analogue, inhibits viral replication in vitro at the nanomolar level, comparable to that of the anti‐influenza drug zanamivir. Using protein X‐ray crystallography we show that the sialosyl α‐sulfonate template binds within the sialidase active site in a ¹C₄ chair conformation. The C1‐sulfonate moiety forms crucial and strong‐binding interactions with the active site's triarginyl cluster, while the 3‐guanidino moiety interacts significantly with conserved active site residues. This sulfonozanamivir analogue provides a new direction in anti‐influenza virus drug development.

中文翻译：

---

磺扎那米韦类似物具有有效的抗流感病毒活性

流感病毒感染继续在世界范围内引起严重的，常常是严重的呼吸道疾病。抗流感药物开发的有效目标是病毒表面蛋白唾液酸酶。在当前的研究中，我们基于一种新的唾液酸磺酸盐模板发现了一种高效的流感病毒唾液酸酶抑制剂。合成的3-胍基唾液酸α-磺酸盐（一种磺扎那米韦类似物）可在纳摩尔水平上抑制体外病毒复制，与抗流感药物扎那米韦相当。使用蛋白质X射线晶体学，我们显示了唾液酸α-磺酸盐模板在¹ C _4中的唾液酸酶活性位点内结合椅子的构型。C1-磺酸盐部分与活性位点的三精氨酰基簇形成关键且牢固的结合相互作用，而3-胍基部分与保守的活性位点残基显着相互作用。该磺酰扎那米韦类似物为抗流感病毒药物的开发提供了新的方向。