Mtemeli Floryn Lynorah, Shoko Ryman, Ndlovu Joice, Mugumbate Grace
Department of Biology, School of Natural Sciences and Mathematics, Chinhoyi University of Technology, Chinhoyi, Zimbabwe.
Department of Chemical Technology, Midlands State University, Gweru, Zimbabwe.
Bioinform Biol Insights. 2022 May 20;16:11779322221100741. doi: 10.1177/11779322221100741. eCollection 2022.
Schistosomiasis, a disease usually related to poverty and poor sanitation, affects more than 200 million people worldwide. Since the 1970s, the medical sector has depended on a single drug, praziquantel, for the treatment of the disease. The emerging evidence of resistance of the Schistosoma parasite to praziquantel and the drug's inefficacy against juvenile stages of the parasite makes the need to find alternative drugs an urgent matter. In this study, we explored the inhibition potential of compounds from using molecular docking studies on purine nucleoside phosphorylase (PNP) and 28-kDa glutathione S-transferase (28kDaGST). Following molecular docking studies and analysis of the active sites, the primary amino acids that were observed and shown to be involved in the PNP-ligand interaction are CYS 33, ARG 86, HIS 88, TYR 90, ALA 118, ALA 119, PRO 200, TYR 202, GLU 203, VAL 219, MET 221, THR 244, ASN 245, PRO 257 and HIS 259. For the 8dKa-ligand interaction, the primary amino acids were PHE 11, ARG 16, TRP 41, LEU 53, GLU 70 and SER 71. Momordicoside I aglycone binds to PNP with the lowest binding affinity of -7.9 kcal/mol by pi sigma bond interactions with HIS 88. Balsaminoside B binds to 28kDaGST with a binding affinity of -7.6 kcal/mol by hydrogen bond interaction with TRP 41, LEU 53 and SER 71. Pharmacokinetic studies showed favourable drug-like properties for the 10 compounds that exhibited the lowest binding energies. Therefore, we propose that bioactive compounds from be considered as potential novel drug hits in the treatment of schistosomiasis.
血吸虫病通常与贫困和卫生条件差有关，全球有超过2亿人受其影响。自20世纪70年代以来，医疗部门一直依赖单一药物吡喹酮来治疗这种疾病。血吸虫寄生虫对吡喹酮产生耐药性的新证据以及该药物对寄生虫幼体阶段无效，使得寻找替代药物成为当务之急。在本研究中，我们通过对嘌呤核苷磷酸化酶（PNP）和28 kDa谷胱甘肽S-转移酶（28kDaGST）进行分子对接研究，探索了[具体来源未提及]化合物的抑制潜力。经过分子对接研究和活性位点分析，观察到并显示参与PNP-配体相互作用的主要氨基酸有CYS 33、ARG 86、HIS 88、TYR 90、ALA 118、ALA 119、PRO 200、TYR 202、GLU 203、VAL 219、MET 221、THR 244、ASN 245、PRO 257和HIS 259。对于8dKa-配体相互作用，主要氨基酸有PHE 11、ARG 16、TRP 41、LEU 53、GLU 70和SER 71。苦瓜苷I苷元通过与HIS 88的π-σ键相互作用，以-7.9 kcal/mol的最低结合亲和力与PNP结合。苦瓜苷B通过与TRP 41、LEU 53和SER 71的氢键相互作用，以-7.6 kcal/mol的结合亲和力与28kDaGST结合。药代动力学研究表明，表现出最低结合能的10种化合物具有良好的类药性质。因此，我们建议将[具体来源未提及]中的生物活性化合物视为治疗血吸虫病的潜在新型药物靶点。
