Bappy Md Nazmul Islam, Ahmed Foeaz, Lasker Tahera, Sajib Emran Hossain, Islam Md Shariful
Faculty of Biotechnology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
Department of Molecular Biology and Genetic Engineering, Sylhet Agricultural University, Sylhet 3100, Bangladesh.
Curr Res Microb Sci. 2024 Oct 19;7:100291. doi: 10.1016/j.crmicr.2024.100291. eCollection 2024.
causes whooping cough in humans that spreads directly from individual to individual mainly by aerosolized respiratory droplets. Nowadays, it gained the attention of scientific community because it has already been reemerged as one of the major public health threats despite widespread vaccination efforts. Moreover, the growing antibiotic resistance has made it difficult to combat this pathogen with currently available antibiotics. Consequently, screening drug targets and discovering drugs against unique proteins of the pathogen could be a promising alternative. With this view, 3,359 proteins of were screened in silico to identify non-duplicate proteins crucial for survival of the bacteria, non-homologous to humans, involved in unique metabolic pathways of the pathogen, and conserved among various bacterial strains. Among these, Chemotaxis protein Mota, Chromosomal replication initiator protein DnaA, Short-chain fatty acids transporter, [protein-PII] uridylyltransferase, Type III secretion protein V, Potassium-transporting ATPase potassium-binding subunit, N-acetylmuramoyl-L-alanine amidase, and RNA polymerase sigma-54 factor fulfilled these criteria. These proteins were further analyzed for qualitative characteristics such as virulence properties and associations with antibiotic resistance, etc. In addition, plant metabolites were screened against these unique proteins utilizing molecular docking to discover putative drugs against them. Four metabolites exhibited superior binding affinity and favorable ADME (Adsorption, distribution, metabolism, and excretion) properties which can further be tested in vivo.
在人类中引发百日咳，主要通过雾化的呼吸道飞沫在个体之间直接传播。如今，它已引起科学界的关注，因为尽管进行了广泛的疫苗接种努力，但它已再度成为主要的公共卫生威胁之一。此外，日益增长的抗生素耐药性使得用目前可用的抗生素对抗这种病原体变得困难。因此，筛选药物靶点并发现针对该病原体独特蛋白质的药物可能是一种有前景的替代方法。基于此观点，对[具体细菌名称]的3359种蛋白质进行了计算机模拟筛选，以鉴定对细菌生存至关重要、与人类无同源性、参与病原体独特代谢途径且在各种细菌菌株中保守的非重复蛋白质。其中，趋化蛋白Mota、染色体复制起始蛋白DnaA、短链脂肪酸转运蛋白、[蛋白-PII]尿苷酰转移酶、III型分泌蛋白V、钾转运ATP酶钾结合亚基、N-乙酰胞壁酰-L-丙氨酸酰胺酶和RNA聚合酶sigma-54因子符合这些标准。对这些蛋白质进一步分析其毒力特性和与抗生素耐药性的关联等定性特征。此外，利用分子对接针对这些独特蛋白质筛选植物代谢物，以发现针对它们的潜在药物。四种代谢物表现出优异的结合亲和力和良好的ADME（吸收、分布、代谢和排泄）特性，可进一步在体内进行测试。
