Abstract: The current pandemic caused by the COVID-19 disease has reached everywhere in the world and has affected every aspect of our lives. As of the current data, the World Health Organization (WHO) has reported more than 300 million confirmed COVID-19 cases worldwide and more than 5 million deaths. M^pro is an enzyme that plays a key role in the life cycle of the SARS-CoV-2 virus, and it is vital for the disease progression. The M^pro enzyme seems to have several allosteric sites that can hinder the enzyme catalytic activity. Furthermore, some of these allosteric sites are located at or nearby the dimerization interface which is essential for the overall M^pro activity. In this review paper, we investigate the potential of the M^pro allosteric site to act as a drug target, especially since they interestingly appear to be resistant to mutation. The work is illustrated through three subsequent sections: First, the two main categories of M^pro allosteric sites have been explained and discussed. Second, a total of six pockets have been studied and evaluated for their druggability and cavity characteristics. Third, the experimental and computational attempts for the discovery of new allosteric inhibitors have been illustrated and discussed. To sum up, this review paper gives a detailed insight into the feasibility of developing new M^pro inhibitors to act as a potential treatment for the COVID-19 disease.
Graphical Abstract:

Keywords: COVID-19, M^pro, SARS-CoV-2, allosteric sites, druggability, antiviral


中文翻译：

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SARS-CoV-2 主要蛋白酶的变构结合位点：广谱抗冠状病毒药物的潜在靶点

摘要：当前由 COVID-19 疾病引起的大流行已经蔓延到世界各地，影响了我们生活的方方面面。截至目前的数据，世界卫生组织 (WHO) 报告了全球超过 3 亿例确诊的 COVID-19 病例和超过 500 万例死亡。M ^pro是一种酶，在 SARS-CoV-2 病毒的生命周期中起关键作用，对疾病进展至关重要。M ^pro酶似乎有几个可以阻碍酶催化活性的变构位点。此外，这些变构位点中的一些位于二聚化界面处或附近，这对整体 M ^pro活性至关重要。在这篇评论文章中，我们调查了 M ^pro的潜力变构位点作为药物靶点，特别是因为它们有趣地似乎对突变具有抗性。这项工作通过三个后续部分进行说明：首先，解释和讨论了M ^{pro变构位点的两个主要类别。}其次，总共研究和评估了六个口袋的成药性和空腔特性。第三，已经说明和讨论了发现新变构抑制剂的实验和计算尝试。综上所述，这篇综述文章详细介绍了开发新的 M ^pro抑制剂作为 COVID-19 疾病潜在治疗方法的可行性。
图形摘要：

关键词： COVID-19，M ^pro, SARS-CoV-2, 变构位点, 成药性, 抗病毒