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关于SARS-CoV和SARS-CoV-2 3CL的杂环抑制剂的最新重点综述

An Updated and Focused Review on Heterocyclic Inhibitors for SARSCoV and SARS-CoV-2 3CL.

作者信息

Manaithiya Ajay, Alam Ozair, Mittal Shruti, Naim Mohd Javed, Imran Mohd, Alshrari Ahmed Subeh, Sheikh Aadil A, Khan Imran A

机构信息

Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.

出版信息

Mini Rev Med Chem. 2023;23(5):576-632. doi: 10.2174/1389557522666220511125102.

Abstract

BACKGROUND

SARS-CoV and SARS-CoV-2 are exceedingly contagious and typically result in major respiratory illnesses (acute respiratory syndrome). The public health is facing enormous challenges across all the nations due to these newly emerging pathogens. Reliable and systematic examination of SARS-CoV and COVID-19 will assist in identifying infectious persons accurately. Based on the biological, chemical, and genetic link of SARS CoV-2 towards SARS-CoV, the recurrence of different anti-SARS-CoV natural drug molecules may be beneficial in the advancement of anti-COVID-19 herbal drug molecules. Here in this review, we evaluated SAR research that has recently been published as well as molecular docking analysis of previously synthesised compounds that have been targeted against SARS-CoV and SARS-CoV-2, respectively. This investigation might assist scientists in creating novel and revolutionary molecules that could target SAR-CoV-2.

OBJECTIVES

The review highlights the heterocyclic inhibitors' ability to successfully inhibit SARSCoV and SARS-CoV-2. The meticulously described structure-activity relationship of potential SARS-CoV and SARS-CoV-2 inhibiting compounds has been addressed in this review.

EVIDENCE ACQUISITION

We conducted a thorough literature assessment employing electronic databases for scientific articles highlighting potential heterocyclic inhibitors for SARS-CoVand SARSCoV- 2, published from 2010 to 2021. We recovered 415 articles, but only 220 were involved and conversed in this manuscript. The article apprehended appropriate research considering three areas: 1) SAR activity, 2) Molecular docking, and 3) Biological activity and future prospects on SARS-CoV-2.

METHODS

The potential compounds with decent inhibitory activity have been discussed and reviewed along with their inhibition potential, expressed in terms of IC value.

RESULTS

Heterocyclic scaffolds reflect an extensive spectrum of therapeutic activity and might function as an initiating concept for the designing and discovery of potential inhibitors for SARS-CoV and SARS-CoV-2 treatment.

CONCLUSION

The points highlighted here may prove to be a vital tool for medicinal chemists working/ investigating more potent and efficacious scaffolds in treating SARS-CoV and SARS-CoV-2.

摘要

背景

严重急性呼吸综合征冠状病毒(SARS-CoV)和新型冠状病毒(SARS-CoV-2)具有极强的传染性,通常会引发严重的呼吸系统疾病(急性呼吸综合征)。由于这些新出现的病原体,全球公共卫生面临着巨大挑战。对SARS-CoV和新型冠状病毒肺炎(COVID-19)进行可靠且系统的检测将有助于准确识别感染者。基于SARS-CoV-2与SARS-CoV的生物学、化学和基因联系,不同抗SARS-CoV天然药物分子的重现可能有助于抗COVID-19草药药物分子的研发。在本综述中,我们评估了最近发表的构效关系(SAR)研究以及之前分别针对SARS-CoV和SARS-CoV-2合成的化合物的分子对接分析。这项研究可能有助于科学家创造出能够靶向SARS-CoV-2的新型革命性分子。

目的

本综述强调了杂环抑制剂成功抑制SARS-CoV和SARS-CoV-2的能力。本综述还探讨了潜在的SARS-CoV和SARS-CoV-2抑制化合物详细描述的构效关系。

证据获取

我们利用电子数据库对2010年至2021年发表的强调潜在SARS-CoV和SARS-CoV-2杂环抑制剂的科学文章进行了全面的文献评估。我们检索到415篇文章,但本手稿仅涉及并讨论了220篇。本文考虑了三个领域进行了适当的研究:1)构效活性,2)分子对接,3)SARS-CoV-2的生物学活性和未来前景。

方法

讨论并综述了具有良好抑制活性的潜在化合物及其以半数抑制浓度(IC值)表示的抑制潜力。

结果

杂环骨架展现出广泛的治疗活性,可能作为设计和发现用于治疗SARS-CoV和SARS-CoV-2的潜在抑制剂的起始概念。

结论

这里强调的要点可能被证明是药物化学家在研究更有效和高效的骨架以治疗SARS-CoV和SARS-CoV-2时的重要工具。

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