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Target-Based Virtual Screening and LC/MS-Guided Isolation Procedure for Identifying Phloroglucinol-Terpenoid Inhibitors of SARS-CoV-2
- Source :
- Journal of Natural Products
- Publication Year :
- 2022
- Publisher :
- American Chemical Society (ACS), 2022.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15206025 and 01633864
- Volume :
- 85
- Database :
- OpenAIRE
- Journal :
- Journal of Natural Products
- Accession number :
- edsair.doi.dedup.....d125e2b92a5f7074bac1108021c34ff5