Abstract：
The capsule is a major virulence factor for Streptococcus pneumoniae which causes global morbidity and mortality. It is already known that there are few conserved genes in the capsular biosynthesis pathway, which are common among all known serotypes, called CpsA, CpsB, CpsC and CpsD. Inhibiting capsular synthesis can render S. pneumoniae defenseless and vulnerable to phagocytosis. The Inhibitory potential of active Zingiber officinale compounds was investigated against the 3D (3-dimensional) structural products of Cps genes using in silico techniques. A 3D compound repository was created and screened for drug-likeness and the qualified compounds were used for molecular docking and dynamic simulation-based experiments using gallic acid for outcome comparison. Cavity-based docking revealed five different cavities in the CpsA, CpsB and CpsD proteins, with gallic acid and selected compounds of Zingiber in a binding affinity range of -6.8 to -8.8 kcal/mol. Gingerenone A, gingerenone B, isogingerenone B and gingerenone C showed the highest binding affinities for CpsA, CpsB and CpsD, respectively. Through the Molegro Virtual Docker re-docking strategy, the highest binding energies (-126.5 kcal/mol) were computed for CpsB with gingerenone A and CpsD with gingerenone B. These findings suggest that gingerenone A, B and C are potential inhibitors of S. pneumoniae-conserved capsule-synthesizing proteins.
摘要：
胶囊是导致全球发病率和死亡率的肺炎链球菌的主要毒力因子。众所周知，在荚膜生物合成途径中很少有保守基因，在所有已知的血清型中都很常见，叫做CpsA，CpsB,CpsC和CpsD.抑制荚膜合成可以使肺炎链球菌无防御能力并且易受吞噬作用的影响。使用计算机技术研究了活性姜化合物对Cps基因的3D（3维）结构产物的抑制潜力。创建了3D化合物库并筛选了药物相似性，并将合格的化合物用于分子对接和基于动态模拟的实验，使用没食子酸进行结果比较。基于腔的对接在CpsA中揭示了五个不同的腔，CpsB和CpsD蛋白，与没食子酸和选定的生姜化合物的结合亲和力范围为-6.8至-8.8kcal/mol。GingerenoneA,GingerenoneB,异基因酮B和金基因酮C对CpsA的结合亲和力最高，CpsB和CpsD,分别。通过Molegro虚拟Docker重新对接策略，用GingerenoneA计算CpsB和用GingerenoneB计算CpsD的最高结合能（-126.5kcal/mol）。这些发现表明，GingerenoneA，B和C是肺炎链球菌保守的囊合成蛋白的潜在抑制剂。
