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金属治疗 COVID-19。利用基于金属的化合物发现新的抗病毒药物。

Metallo therapeutics for COVID-19. Exploiting metal-based compounds for the discovery of new antiviral drugs.

机构信息

Department of Chemistry and Industrial Chemistry, University of Pisa , Pisa, Italy.

Laboratory of Metals in Medicine (Metmed), Department of Chemistry "U. Schiff", University of Florence , Sesto Fiorentino, Italy.

出版信息

Expert Opin Drug Discov. 2021 Jan;16(1):39-46. doi: 10.1080/17460441.2020.1819236. Epub 2020 Sep 11.

Abstract

INTRODUCTION

The COVID-19 pandemic poses an unprecedented challenge for the rapid discovery of drugs against this life-threatening disease. Owing to the peculiar features of the metal centers that are currently used in medicinal chemistry, metallodrugs might offer an excellent opportunity to achieve this goal.

AREAS COVERED

Two main strategies for developing metal-based drugs against the SARS-CoV-2 are herein illustrated. Firstly, a few clinically approved metallodrugs could be evaluated in patients according to a 'drug repurposing' approach. To this respect, the gold drug auranofin seems a promising candidate, but some other clinically established metal compounds are worthy of a careful evaluation as well. On the other hand, libraries of inorganic compounds, featuring a large chemical diversity, should be screened to identify the most effective molecules. This second strategy might be assisted by a pathway-driven discovery approach arising from a preliminary knowledge of the mode of action, exploitable to inhibit the functional activities of the key viral proteins. Also, attention must be paid to selectivity and toxicity issues.

EXPERT OPINION

The medicinal inorganic chemistry community may offer a valuable contribution against COVID-19. The screening of metallodrugs' libraries can expand the explored 'chemical space' and increase the chance of finding effective anti-COVID agents.

摘要

简介

COVID-19 大流行给快速发现针对这种危及生命疾病的药物带来了前所未有的挑战。由于目前在药物化学中使用的金属中心的特殊特征,金属药物可能为实现这一目标提供极好的机会。

涵盖领域

本文阐述了开发针对 SARS-CoV-2 的基于金属的药物的两种主要策略。首先,可以根据“药物再利用”方法在患者中评估少数临床批准的金属药物。在这方面,金药物金诺芬似乎是一个有前途的候选药物,但其他一些临床上已确立的金属化合物也值得仔细评估。另一方面,应筛选具有丰富化学多样性的无机化合物库,以鉴定最有效的分子。第二种策略可以通过初步了解作用模式而产生的基于途径的发现方法来辅助,可利用该方法来抑制关键病毒蛋白的功能活性。此外,还必须注意选择性和毒性问题。

专家意见

药用无机化学界可能会为对抗 COVID-19 做出有价值的贡献。筛选金属药物库可以扩大探索的“化学空间”,并增加找到有效抗 COVID 药物的机会。

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