Unveiling <i>Taenia solium</i> kinome profile and its potential for new therapeutic targets

<b>Background</b>: Helminth infections cause widespread morbidity and are a significant global disease burden. One among them is Neurocysticercosis, a central nervous system infection caused by the larvae <i>Taenia solium</i>, leading to epilepsy. Helminths are strong immune modulators and can survive for a long time in adverse host environments. Kinases are molecular switches and are essential to initiate/propagate signaling cascades and are detrimental to the regulation of homeostasis. They have been implicated in the progression of many diseases and are potentially lucrative drug targets. <b>Objective</b>: To identify kinases in <i>T. solium</i> proteome and prioritize them as drug targets. <b>Methodology</b>: A Hidden Markov Model (HMM) was used to curate and classify kinases into families based on sequence homology to model organisms followed by phylogenetic analysis of each family. To predict potential drug targets, kinases were identified based on a homologically lethal relationship to <i>C. elegans</i> but non-lethal to humans. Kinases thus selected were searched for matching ligands in SARFkinase and DrugBank databases. <b>Result and conclusion</b>: <i>T. solium</i> kinases make up 1.8% of its proteome, CMGC is the largest kinase family and RGC is the smallest and catalytically inactive family. We predict 23-potential kinases to be drug targets for <i>T. solium</i>.<b>背景</b>：蠕虫感染可引发广泛病症，造成沉重的全球疾病负担。其中一类为神经囊尾蚴病（Neurocysticercosis），是由猪带绦虫（Taenia solium）幼虫引发的中枢神经系统感染，可导致癫痫发作。蠕虫属于强效免疫调节剂，能够在宿主的不利环境中长期存活。激酶作为分子开关，是启动/传递信号级联反应的关键元件，且对体内稳态的调控具有不利影响，其与多种疾病的进展密切相关，是极具潜力的药物靶点。<b>目的</b>：旨在鉴定猪带绦虫（Taenia solium）蛋白质组中的激酶，并将其筛选为优先药物靶点。<b>研究方法</b>：本研究采用隐马尔可夫模型（Hidden Markov Model, HMM），基于与模式生物的序列同源性对激酶进行注释与家族分类，随后对每个激酶家族开展系统发育分析。为预测潜在药物靶点，本研究以与秀丽隐杆线虫（Caenorhabditis elegans, C. elegans）存在同源致死关系、且对人类无致死性作为筛选标准，鉴定目标激酶。随后在SARFkinase与DrugBank数据库中检索上述筛选得到的激酶的匹配配体。<b>结果与结论</b>：猪带绦虫的激酶占其蛋白质组的1.8%；CMGC家族为最大的激酶家族，RGC家族则是最小且无催化活性的激酶家族。本研究预测共23种激酶可作为猪带绦虫的潜在药物靶点。