Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India.
Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
Adv Protein Chem Struct Biol. 2020;121:237-251. doi: 10.1016/bs.apcsb.2019.11.012. Epub 2019 Dec 18.
Antibiotics are therapeutic agents against bacterial infections, however, the emergence of multiple and extremely drug-resistant microbes (Multi-Drug Resistant and Extremely Drug-Resistant) are compromising the effectiveness of the currently available treatment options. The drug resistance is not a novel crisis, the current pace of drug discovery has failed to compete with the growth of MDR and XDR pathogenic strains and therefore, it is highly central to find out novel antimicrobial drugs with unique mechanisms of action which may reduce the burden of MDR and XDR pathogenic strains. Protein-protein interactions (PPIs) are involved in a countless of the physiological and cellular phenomena and have become an attractive target to treat the diseases. Therefore, targeting PPIs in infectious agents may offer a completely novel strategy of intervention to develop anti-infective drugs that may combat the ever-increasing rate of drug resistant strains. This chapter describes how small molecule candidate inhibitors that are capable of disrupting the PPIs in pathogenic microbes and it could be an alternative lead discovery strategy to obtain novel antibiotics. Over the last three decades, there has been increasing efforts focused on the manipulation of PPIs in order to develop novel therapeutic interventions. The diversity and complexity of such a complex and highly dynamic systems pose many challenges in targeting PPIs by drug-like molecules with necessary selectivity and potency. Traditional and novel drug discovery strategies have provided tools for designing and assessing PPI inhibitors against infectious diseases.
抗生素是针对细菌感染的治疗药物，然而，多种和极其耐药的微生物（多药耐药和极耐药）的出现正在影响目前可用治疗方案的有效性。耐药性并不是一个新的危机，目前的药物发现速度未能与 MDR 和 XDR 病原菌的增长相抗衡，因此，寻找具有独特作用机制的新型抗菌药物以减少 MDR 和 XDR 病原菌的负担至关重要。蛋白质-蛋白质相互作用（PPIs）参与了无数的生理和细胞现象，已成为治疗疾病的有吸引力的靶点。因此，针对感染性病原体中的 PPIs 可能提供一种全新的干预策略，以开发能够对抗不断增加的耐药菌株的抗感染药物。本章描述了能够破坏病原微生物中 PPIs 的小分子候选抑制剂，这可能是获得新型抗生素的替代先导发现策略。在过去的三十年中，人们越来越关注操纵 PPIs 以开发新型治疗干预措施。这种复杂且高度动态系统的多样性和复杂性给用具有必要选择性和效力的类药分子靶向 PPIs 带来了许多挑战。传统和新型药物发现策略为针对传染病设计和评估 PPI 抑制剂提供了工具。
