Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, PU, Italy.
Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, CA, Italy.
Int J Mol Sci. 2022 Jan 4;23(1):545. doi: 10.3390/ijms23010545.
Despite the great strides in healthcare during the last century, some challenges still remained unanswered. The development of multi-drug resistant bacteria, the alarming growth of fungal infections, the emerging/re-emerging of viral diseases are yet a worldwide threat. Since the discovery of natural antimicrobial peptides able to broadly hit several pathogens, peptide-based therapeutics have been under the lenses of the researchers. This review aims to focus on synthetic peptides and elucidate their multifaceted mechanisms of action as antiviral, antibacterial and antifungal agents. Antimicrobial peptides generally affect highly preserved structures, e.g., the phospholipid membrane via pore formation or other constitutive targets like peptidoglycans in Gram-negative and Gram-positive bacteria, and glucan in the fungal cell wall. Additionally, some peptides are particularly active on biofilm destabilizing the microbial communities. They can also act intracellularly, e.g., on protein biosynthesis or DNA replication. Their intracellular properties are extended upon viral infection since peptides can influence several steps along the virus life cycle starting from viral receptor-cell interaction to the budding. Besides their mode of action, improvements in manufacturing to increase their half-life and performances are also taken into consideration together with advantages and impairments in the clinical usage. Thus far, the progress of new synthetic peptide-based approaches is making them a promising tool to counteract emerging infections.
尽管上个世纪在医疗保健方面取得了巨大进展，但仍有一些挑战尚未得到解决。多药耐药菌的发展、真菌性感染的惊人增长、新出现/再次出现的病毒性疾病仍然是全球威胁。自从发现能够广泛攻击多种病原体的天然抗菌肽以来，基于肽的治疗方法一直受到研究人员的关注。本综述旨在重点关注合成肽，并阐明其作为抗病毒、抗菌和抗真菌剂的多效作用机制。抗菌肽通常会影响高度保守的结构，例如通过形成孔或其他组成型靶标（如革兰氏阴性和革兰氏阳性菌中的肽聚糖和真菌细胞壁中的葡聚糖）影响磷脂膜。此外，一些肽对破坏生物膜特别有效，从而破坏微生物群落。它们还可以在细胞内发挥作用，例如，影响蛋白质生物合成或 DNA 复制。它们的细胞内特性在病毒感染时会进一步扩展，因为肽可以影响病毒生命周期的几个步骤，从病毒与细胞的相互作用到出芽。除了它们的作用模式外，还考虑了提高其半衰期和性能的制造改进，以及在临床使用中的优势和缺陷。到目前为止，新的基于合成肽的方法的进展使它们成为对抗新出现的感染的有前途的工具。
