Functional and druggability analysis of the SARS-CoV-2 proteome.
Functional and druggability analysis of the SARS-CoV-2 proteome.
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DOI：
10.1016/j.ejphar.2020.173705
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发表时间：
2021-01-05
影响因子：
5
通讯作者：
Maggini J
中科院分区：
文献类型：
--
作者：
Cavasotto CN;Lamas MS;Maggini J
由冠状病毒SARS-CoV-2引起的传染性冠状病毒病（COVID-19）大流行于2019年12月在中国武汉出现，并已蔓延至全球。截至今天，已有4 600多万人受到感染，120多万人死亡。为了有助于开发有效的治疗方法，我们在计算机上确定了结合热点，并评估了它们在完整的SARS-CoV-2蛋白质组中的可药用性。所有的结构，非结构，和辅助蛋白进行了研究，当SARS-CoV-2蛋白的实验结构数据不可用时，同源性模型建立在解决SARS-CoV结构的基础上。在不同的病毒靶点上鉴定了几个潜在的变构或蛋白质-蛋白质相互作用的可药物化位点，这些知识可用于将当前的药物发现努力扩展到目前探索的半胱氨酸蛋白酶和聚合酶复合物之外。我们希望这项研究将支持科学界在理解这种疾病的分子决定因素和扩大病毒靶点以寻求针对COVID-19的重新用途或新型药物方面的努力。
The infectious coronavirus disease (COVID-19) pandemic, caused by the coronavirus SARS-CoV-2, appeared in December 2019 in Wuhan, China, and has spread worldwide. As of today, more than 46 million people have been infected and over 1.2 million fatalities. With the purpose of contributing to the development of effective therapeutics, we performed an in silico determination of binding hot-spots and an assessment of their druggability within the complete SARS-CoV-2 proteome. All structural, non-structural, and accessory proteins have been studied, and whenever experimental structural data of SARS-CoV-2 proteins were not available, homology models were built based on solved SARS-CoV structures. Several potential allosteric or protein-protein interaction druggable sites on different viral targets were identified, knowledge that could be used to expand current drug discovery endeavors beyond the currently explored cysteine proteases and the polymerase complex. It is our hope that this study will support the efforts of the scientific community both in understanding the molecular determinants of this disease and in widening the repertoire of viral targets in the quest for repurposed or novel drugs against COVID-19.
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