Target-Based Virtual Screening and LC/MS-Guided Isolation Procedure for Identifying Phloroglucinol-Terpenoid Inhibitors of SARS-CoV-2
| Autor: | Bo Hou, Yu-Min Zhang, Han-Yi Liao, Li-Feng Fu, De-Dong Li, Xin Zhao, Jian-Xun Qi, Wei Yang, Geng-Fu Xiao, Lian Yang, Zheng-Yu Zuo, Lin Wang, Xiang-Lei Zhang, Fang Bai, Liu Yang, George F. Gao, Hao Song, Jiang-Miao Hu, Wei-Juan Shang, Jun Zhou |
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| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
Biological Products Dryopteris Magnetic Resonance Spectroscopy Molecular Structure SARS-CoV-2 Terpenes Organic Chemistry Virtual Reality Pharmaceutical Science Microbial Sensitivity Tests Phloroglucinol Crystallography X-Ray Antiviral Agents Mass Spectrometry Article Analytical Chemistry Molecular Docking Simulation Drug Delivery Systems Complementary and alternative medicine Drug Discovery Molecular Medicine Chromatography High Pressure Liquid Chromatography Liquid |
| Zdroj: | Journal of Natural Products |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/acs.jnatprod.1c00805 |
| Popis: | The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 5 million deaths worldwide to date. Due to the limited therapeutic options so far available, target-based virtual screening with LC/MS support was applied to identify the novel and high-content compounds 1–4 with inhibitory effects on SARS-CoV-2 in Vero E6 cells from the plant Dryopteris wallichiana. These compounds were also evaluated against SARS-CoV-2 in Calu-3 cells and showed unambiguous inhibitory activity. The inhibition assay of targets showed that compounds 3 and 4 mainly inhibited SARS-CoV-2 3CLpro, with effective Kd values. Through docking and molecular dynamics modeling, the binding site is described, providing a comprehensive understanding of 3CLpro and interactions for 3, including hydrogen bonds, hydrophobic bonds, and the spatial occupation of the B ring. Compounds 3 and 4 represent new, potential lead compounds for the development of anti-SARS-CoV-2 drugs. This study has led to the development of a target-based virtual screening method for exploring the potency of natural products and for identifying natural bioactive compounds for possible COVID-19 treatment. |
| Databáze: | OpenAIRE |
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