Identified a novel preventive agents for infective endocarditis

感染性心内膜炎是一种心脏瓣膜的感染，它会导致心脏内层的植被形成、败血症和血栓栓塞。虽然感染性心内膜炎发生在表面健康的人群中，但某些先天性心脏缺陷会增加其风险。然后，需要对有出血的高危患者在用药前给予抗菌药物。不幸的是，在牙科治疗前使用抗菌剂几乎没有效果。在这项研究中，我们发现了一种新的预防感染性心内膜炎的药物。戈多氏链球菌是一种绿绿链球菌，是人类口腔正常菌群的组成部分。它在牙菌斑的形成过程中起着重要的拓荒者作用。此外，gordonii也因其定植受损心脏瓣膜的能力而闻名，并且是最常被鉴定为感染性心内膜炎的主要病原细菌。Hsa是gordonii的表面蛋白，与含α2-3链唾液酸的蛋白结合，参与感染性心内膜炎的发病。本研究鉴定了一种抑制Hsa唾液酸结合活性的新化合物。为了鉴定Hsa抑制剂，我们使用血凝试验筛选了9600种化合物。我们在筛选中确定了3种化合物作为初始hit。接下来，我们检测了它们对GST-HsaNR2与3 ' -唾液基乳糖结合的抑制活性。在这些候选化合物中，2号化合物表现出更强的Hsa抑制活性。在这项研究中，我们从化学文库中获得了一个候选化合物。

Infective endocarditis is an infection of the heart valves that causes the vegetation formation on the inner layer of the heart, sepsis, and thromboembolism. While infective endocarditis occurs in apparently healthy people, certain congenital heart defects increase its risk. Then, it needs to administrate of antibacterial agents to high-risk patient before medical treatment accompanied with bleeding. Unfortunately, there are few effects of administration of antibacterial agents before dental treatment. In this study, we identified a novel preventive agent for infective endocarditis. Streptococcus gordonii is one of viridans group streptococci and component of the normal microbial flora of human oral cavity. It plays significant roles as pioneer colonizers in the development of dental plaque. In addition, S. gordonii is also well known for its ability to colonize damaged heart valves and is the most frequently identified bacteria as primary etiological agents of infective endocarditis. An Hsa, is a surface protein of S. gordonii and binds to α2-3-link sialic acid-containing proteins, contributes to pathogenesis of infective endocarditis. In present study, we identified a novel compound to inhibit Hsa sialic acid binding activity. To identify Hsa inhibitors, we performed a screening of 9600 compounds by using hemagglutination assay. We identified 3 compounds as initial hits in the screening. Next, we examined their inhibition activity of GST-HsaNR2 binding to 3’-sialyllactose. Among these candidate compounds, No.2 showed more potent Hsa inhibition activity. In this study, we obtained one of candidate compound from chemical library.