Rangel Karyne, Lechuga Guilherme Curty, Provance David W, Morel Carlos M, De Simone Salvatore G
Center for Technological Development in Health (CDTS), National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswaldo Cruz Institut, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil.
Epidemiology and Molecular Systematics Laboratory (LEMS), Oswaldo Cruz Institut, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil.
Pharmaceuticals (Basel). 2023 Sep 11;16(9):1281. doi: 10.3390/ph16091281.
The rise in antibiotic-resistant strains of clinically important pathogens is a major threat to global health. The World Health Organization (WHO) has recognized the urgent need to develop alternative treatments to address the growing list of priority pathogens. Antimicrobial peptides (AMPs) rank among the suggested options with proven activity and high potential to be developed into effective drugs. Many AMPs are naturally produced by living organisms protecting the host against pathogens as a part of their innate immunity. Mechanisms associated with AMP actions include cell membrane disruption, cell wall weakening, protein synthesis inhibition, and interference in nucleic acid dynamics, inducing apoptosis and necrosis. is a critical pathogen, as severe clinical implications have developed from isolates resistant to current antibiotic treatments and conventional control procedures, such as UV light, disinfectants, and drying. Here, we review the natural AMPs representing primary candidates for new anti- drugs in post-antibiotic-era and present computational tools to develop the next generation of AMPs with greater microbicidal activity and reduced toxicity.
临床上重要病原体的抗生素耐药菌株的增加是对全球健康的重大威胁。世界卫生组织(WHO)已认识到迫切需要开发替代疗法,以应对越来越多的优先病原体。抗菌肽(AMPs)是具有已证实活性且极有可能被开发成有效药物的建议选项之一。许多抗菌肽是生物体自然产生的,作为其固有免疫的一部分保护宿主抵御病原体。与抗菌肽作用相关的机制包括细胞膜破坏、细胞壁弱化、蛋白质合成抑制以及对核酸动态的干扰,诱导细胞凋亡和坏死。 是一种关键病原体,因为对当前抗生素治疗以及紫外线、消毒剂和干燥等传统控制程序耐药的分离株已产生了严重的临床影响。在此,我们综述了代表抗生素后时代新型抗 药物主要候选物的天然抗菌肽,并介绍了开发具有更强杀菌活性和更低毒性的下一代抗菌肽的计算工具。