Peraman Ramalingam, Sure Sathish Kumar, Dusthackeer V N Azger, Chilamakuru Naresh Babu, Yiragamreddy Padmanabha Reddy, Pokuri Chiranjeevi, Kutagulla Vinay Kumar, Chinni Santhivardhan
RERDS-CPR, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, Anantapur, Andhra Pradesh India.
ICMR-National Institute of Research in Tuberculosis, Chennai, Tamilnadu India.
Futur J Pharm Sci. 2021;7(1):56. doi: 10.1186/s43094-021-00196-5. Epub 2021 Mar 3.
Despite the various strategies undertaken in the clinical practice, the mortality rate due to antibiotic-resistant microbes has been markedly increasing worldwide. In addition to multidrug-resistant (MDR) microbes, the "ESKAPE" bacteria are also emerging. Of course, the infection caused by ESKAPE cannot be treated even with lethal doses of antibiotics. Now, the drug resistance is also more prevalent in antiviral, anticancer, antimalarial and antifungal chemotherapies.
To date, in the literature, the quantum of research reported on the discovery strategies for new antibiotics is remarkable but the milestone is still far away. Considering the need of the updated strategies and drug discovery approaches in the area of drug resistance among researchers, in this communication, we consolidated the insights pertaining to new drug development against drug-resistant microbes. It includes drug discovery void, gene paradox, transposon mutagenesis, vitamin biosynthesis inhibition, use of non-conventional media, host model, target through quorum sensing, genomic-chemical network, synthetic viability to targets, chemical versus biological space, combinational approach, photosensitization, antimicrobial peptides and transcriptome profiling. Furthermore, we optimally briefed about antievolution drugs, nanotheranostics and antimicrobial adjuvants and then followed by twelve selected new feasible drug targets for new drug design against drug resistance. Finally, we have also tabulated the chemical structures of potent molecules against antimicrobial resistance.
It is highly recommended to execute the anti-drug resistance research as integrated approach where both molecular and genetic research needs to be as integrative objective of drug discovery. This is time to accelerate new drug discovery research with advanced genetic approaches instead of conventional blind screening.
尽管临床实践中采取了各种策略，但全球范围内由抗生素耐药微生物导致的死亡率仍在显著上升。除了多重耐药（MDR）微生物外，“ESKAPE”细菌也在不断出现。当然，即使使用致死剂量的抗生素也无法治疗由ESKAPE引起的感染。如今，耐药性在抗病毒、抗癌、抗疟疾和抗真菌化疗中也更为普遍。
迄今为止，在文献中，关于新抗生素发现策略的研究数量可观，但距离取得重大突破仍很遥远。考虑到研究人员在耐药领域对更新策略和药物发现方法的需求，在本交流中，我们整合了有关针对耐药微生物的新药开发的见解。它包括药物发现空白、基因悖论、转座子诱变、维生素生物合成抑制、非常规培养基的使用、宿主模型、群体感应靶点、基因组-化学网络、对靶点的合成生存能力、化学空间与生物空间、组合方法、光致敏、抗菌肽和转录组分析。此外，我们还对抗进化药物、纳米诊疗学和抗菌佐剂进行了优化介绍，随后列出了针对耐药性设计新药的十二个选定的新可行药物靶点。最后，我们还列出了针对抗菌耐药性的强效分子的化学结构。
强烈建议将抗耐药性研究作为一种综合方法来实施，其中分子和基因研究都需要成为药物发现的综合目标。现在是时候用先进的遗传方法加速新药发现研究，而不是传统的盲目筛选。
