PDF(Pubmed)
Abstract：
Schistosomiasis, otherwise known as bilharzia or snail fever, is a disease that usually affects poor people and people exposed to poor sanitation. The disease affects over 200 million people worldwide annually. Schistosomiasis has been treated using a single drug, praziquantel, since the 1970s and this is resulting in schistosomes becoming resistant. Therefore, there is an urgent need to develop new antischistosoma drugs and vaccines. This study focuses on identifying potential antischistosomal compounds from the plant Salvia fruticosa. We virtually screened a library of 163 S fruticosa compounds by docking against Schistosoma mansoni sulfotransferase (SmSULT) using the PyRx software. Docking scores ranged from -4.7 to -9.3 kcal/mol. Compounds with binding affinity of -7.6 or stronger were subjected to drug-likeness assessments using the DataWarrior software. We also employed the PAINS removal tool to filter off false-positive results. Twelve compounds passed the drug-likeness screen, and these were subjected to in silico toxicity predictions to determine their mutagenic, tumorigenic and reproductive potential. Seven compounds were predicted to be nontoxic. After considering the toxicity analysis results and drug scores of the compounds, we identified rosmarinic acid and hispidulin as qualifying for further evaluation as potential drugs against schistosomiasis. Free energy calculations using the fastDRH webserver and molecular dynamics simulations using CABS-flex showed that the receptor-ligand complexes for the 2 lead compounds are stable under physiological conditions. We recommend that rosmarinic acid and hispidulin be used as hit compounds for the development of potential antischistosomal drugs.
摘要：
血吸虫病,也被称为bilharzia或蜗牛热，是一种通常会影响穷人和卫生条件差的人的疾病。该疾病每年影响全球超过2亿人。血吸虫病已经使用单一药物治疗，吡喹酮,自20世纪70年代以来，这导致血吸虫变得耐药。因此,迫切需要开发新的抗血吸虫药物和疫苗。这项研究的重点是从植物丹参中鉴定潜在的抗血吸虫化合物。我们使用PyRx软件通过与曼氏血吸虫磺基转移酶（SmSULT）对接，实际上筛选了163Sfruitcosa化合物的文库。对接评分范围为-4.7至-9.3kcal/mol。使用DataWarrior软件对具有〜7.6或更强的结合亲和力的化合物进行药物相似性评估。我们还使用了PAINS去除工具来过滤掉假阳性结果。12种化合物通过了药物相似性筛选，并对这些进行了计算机毒性预测，以确定它们的诱变性，致瘤和生殖潜力。预测七种化合物是无毒的。在考虑化合物的毒性分析结果和药物评分后，我们确定迷迭香酸和粘骨素作为潜在的抗血吸虫病药物有资格进一步评估.使用fastDRH网络服务器的自由能计算和使用CABS-flex的分子动力学模拟表明，2个前导化合物的受体-配体复合物在生理条件下是稳定的。我们建议使用迷迭香酸和hispidulin作为开发潜在抗血吸虫药物的化合物。
