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通过氯喹类似物靶向内体酸化作为治疗新出现病毒性疾病的一种有前景的策略。

Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases.

作者信息

Al-Bari Md Abdul Alim

机构信息

Department of Pharmacy University of Rajshahi Rajshahi 6205 Bangladesh.

出版信息

Pharmacol Res Perspect. 2017 Jan 23;5(1):e00293. doi: 10.1002/prp2.293. eCollection 2017 Feb.

Abstract

Emerging viruses such as HIV, dengue, influenza A, SARS coronavirus, Ebola, and other viruses pose a significant threat to human health. Majority of these viruses are responsible for the outbreaks of pathogenic lethal infections. To date, there are no effective therapeutic strategies available for the prophylaxis and treatment of these infections. Chloroquine analogs have been used for decades as the primary and most successful drugs against malaria. Concomitant with the emergence of chloroquine-resistant strains and a subsequent decrease in the use as antimalarial drugs, other applications of the analogs have been investigated. Since the analogs have interesting biochemical properties, these drugs are found to be effective against a wide variety of viral infections. As antiviral action, the analogs have been shown to inhibit acidification of endosome during the events of replication and infection. Moreover, immunomodulatory effects of analogs have been beneficial to patients with severe inflammatory complications of several viral diseases. Interestingly, one of the successful targeting strategies is the inhibition of HIV replication by the analogs in vitro which are being tested in several clinical trials. This review focuses on the potentialities of chloroquine analogs for the treatment of endosomal low pH dependent emerging viral diseases.

摘要

诸如人类免疫缺陷病毒(HIV)、登革热病毒、甲型流感病毒、严重急性呼吸综合征冠状病毒(SARS-CoV)、埃博拉病毒等新兴病毒对人类健康构成了重大威胁。这些病毒中的大多数是致病性致命感染爆发的元凶。迄今为止,尚无有效的治疗策略可用于预防和治疗这些感染。氯喹类似物几十年来一直作为抗疟疾的主要且最成功的药物使用。随着氯喹耐药菌株的出现以及随后作为抗疟药物使用的减少,人们对该类似物的其他应用进行了研究。由于该类似物具有有趣的生化特性,发现这些药物对多种病毒感染有效。作为抗病毒作用,已表明该类似物在复制和感染过程中可抑制内体的酸化。此外,该类似物的免疫调节作用对患有几种病毒性疾病严重炎症并发症的患者有益。有趣的是,成功的靶向策略之一是该类似物在体外抑制HIV复制,目前正在多项临床试验中进行测试。本综述重点关注氯喹类似物治疗内体低pH依赖性新兴病毒性疾病的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca98/5461643/c65063ed5da1/PRP2-5-e00293-g001.jpg

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