Recent Advances in Diagnostics and Therapeutic Interventions for Drug-Resistant Malaria.

IF 3.8 2区 医学 Q2 CHEMISTRY, MEDICINAL
ACS Infectious Diseases Pub Date : 2025-06-13 Epub Date: 2025-05-06 DOI:10.1021/acsinfecdis.4c00962
Kangkana Barman, Pranab Goswami
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Abstract

The emergence of drug-resistant malarial parasites has been a growing challenge to medical science to safeguard public health in the malaria-endemic regions of the globe. With time, the parasite develops newer resistance mechanisms to defunct the drug's action one after another. Genetic mutation is the prime weapon parasites rely upon to initiate the resistance mechanism in a case-specific manner, following various strategies such as structural changes in the target protein, metabolic alterations, and tweaking the drug-transported channels. In order to combat these resistances, different approaches have evolved among these developing inhibitors against critical parasite enzymes and metabolic pathways, combinatorial/hybrid drug therapies, exploring new drug targets and analogues of existing drugs, use of resistance-reversal agents, drug-repurposing, gene blocking/altering using RNA interference and CRISPR/Cas systems are prominent. However, the effectiveness of these approaches needs to be earnestly monitored for better management of the disease, which demands the development of a reliable diagnosis technique. Several methodologies have been investigated in search of a suitable diagnosis technique, such as in vivo, in vitro, ex vivo drug efficacy studies, and molecular techniques. A parallel effort to transform the efficient method into an inexpensive and portable diagnosis tool for rapid screening of drug resistance malaria among masses in the societal landscape is advocated. This review gives an insight into the historical perspectives of drug-resistant malaria and the recent developments in malaria diagnosis and antimalarial drug discovery. Efforts have been made to update recent strategies formulated to combat and diagnose drug-resistant malaria. Finally, a concluding remark with a future perspective on the subject has been forwarded.

耐药疟疾诊断和治疗干预措施的最新进展。
耐药疟疾寄生虫的出现对维护全球疟疾流行地区公众健康的医学科学构成了日益严峻的挑战。随着时间的推移,寄生虫发展出新的耐药机制,使药物的作用一个接一个地失效。基因突变是寄生虫以特定病例的方式启动耐药机制的主要武器,它遵循多种策略,如靶蛋白的结构改变、代谢改变和调整药物运输通道。为了对抗这些耐药性,不同的方法已经在这些针对关键寄生虫酶和代谢途径的抑制剂中发展,组合/混合药物治疗,探索新的药物靶点和现有药物的类似物,使用耐药逆转剂,药物再利用,使用RNA干扰和CRISPR/Cas系统阻断/改变基因。然而,需要认真监测这些方法的有效性,以便更好地管理疾病,这需要开发可靠的诊断技术。为了寻找合适的诊断技术,已经研究了几种方法,如体内、体外、离体药物疗效研究和分子技术。提倡同时努力将这种有效的方法转变为一种廉价和便携式的诊断工具,以便在社会范围内快速筛查大众中的耐药性疟疾。本文综述了耐药疟疾的历史观点以及疟疾诊断和抗疟疾药物发现的最新进展。已作出努力更新最近为防治和诊断耐药疟疾而制定的战略。最后,提出了对这个问题的未来展望的结束语。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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