Raj Sneha, Venugopal Umamageswaran, Pant Garima, Kalyan Mitra, Arockiaraj Jesu, Krishnan Manju Y, Pasupuleti Mukesh
Microbiology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.
Electron Microscopy Unit, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.
Arch Microbiol. 2021 Oct;203(8):4891-4899. doi: 10.1007/s00203-021-02474-5. Epub 2021 Jul 9.
Worldwide, TB is one of the deadly airborne diseases, which accounts for 10.4 million deaths annually. Serious toxicity issue, prolonged treatment regimens of the current drugs, rise in multidrug-resistant strains, and the unique defensive mechanism makes the development of novel therapeutic molecules against Mycobacterium tuberculosis (MT) an urgent need. As MT has a lengthy latent phase and unique cell wall architecture, a reasonable approach is needed to find molecules having a different killing mechanism rather than traditional approaches. Host defence peptides (HDPs) will be the most promising alternative, potential therapeutic candidates as they target the microbial membrane in particular and are an essential part of the innate immunity of humans. This works demonstrates the utility of "Database filtering" and three-dimensional (3D) modelling approach in finding novel AMPs with appreciable activity towards MT. Results of this study indicate that peptides with 70% hydrophobicity, but without hydrophobicity patches (> 4 hydrophobic amino acids in series) and charge of + 4 or + 5 are most likely to be good anti-tubercular candidates.
在全球范围内,结核病是致命的空气传播疾病之一,每年导致1040万人死亡。严重的毒性问题、当前药物的长期治疗方案、多重耐药菌株的增加以及独特的防御机制,使得开发针对结核分枝杆菌(MT)的新型治疗分子成为迫切需求。由于MT具有漫长的潜伏期和独特的细胞壁结构,需要一种合理的方法来寻找具有不同杀伤机制的分子,而不是传统方法。宿主防御肽(HDPs)将是最有前途的替代潜在治疗候选物,因为它们特别靶向微生物膜,并且是人类先天免疫的重要组成部分。这项工作展示了“数据库筛选”和三维(3D)建模方法在寻找对MT具有可观活性的新型抗菌肽方面的效用。这项研究的结果表明,疏水性为70%、但没有疏水补丁(连续>4个疏水氨基酸)且电荷为+4或+5的肽最有可能是良好的抗结核候选物。