Molecular Diversity ( IF 3.9 ) Pub Date : 2021-01-05 , DOI: 10.1007/s11030-020-10166-3 Sk Abdul Amin 1 , Suvankar Banerjee 1 , Samayaditya Singh 2 , Insaf Ahmed Qureshi 2 , Shovanlal Gayen 3 , Tarun Jha 1
|
Abstract
Main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) intervenes in the replication and transcription processes of the virus. Hence, it is a lucrative target for anti-viral drug development. In this study, molecular modeling analyses were performed on the structure activity data of recently reported diverse SARS-CoV-2 Mpro inhibitors to understand the structural requirements for higher inhibitory activity. The classification-based quantitative structure–activity relationship (QSAR) models were generated between SARS-CoV-2 Mpro inhibitory activities and different descriptors. Identification of structural fingerprints to increase or decrease in the inhibitory activity was mapped for possible inclusion/exclusion of these fingerprints in the lead optimization process. Challenges in ADME properties of protease inhibitors were also discussed to overcome the problems of oral bioavailability. Further, depending on the modeling results, we have proposed novel as well as potent SARS-CoV-2 Mpro inhibitors.
Graphic Abstract
中文翻译：
SARS-CoV-2 病毒主要蛋白酶 (Mpro) 抑制剂的首次结构-活性关系分析：COVID-19 药物发现的努力
摘要
严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 的主要蛋白酶 (Mpro) 干预病毒的复制和转录过程。因此，它是抗病毒药物开发的一个利润丰厚的目标。在本研究中，对最近报道的多种 SARS-CoV-2 Mpro 抑制剂的结构活性数据进行了分子建模分析，以了解更高抑制活性的结构要求。在 SARS-CoV-2 Mpro 抑制活性和不同描述符之间生成了基于分类的定量结构-活性关系 (QSAR) 模型。对增加或减少抑制活性的结构指纹的识别进行了映射，以便在先导优化过程中可能包含/排除这些指纹。还讨论了蛋白酶抑制剂 ADME 特性的挑战，以克服口服生物利用度的问题。此外，根据建模结果，我们提出了新型且有效的 SARS-CoV-2 Mpro 抑制剂。
京公网安备 11010802027423号