Natural Product Communications
·
2025
·
IF 1.4
Yongxia Shi,Xiaoning Sun,Zhaoxia Yu,Dalan Dai,Hongyu Guo,Lijuan Mei,Jun Dai,Lei Jiang
ObjectiveBergenia purpurascens, a medicinal herb indigenous to southwestern China, has garnered interest for its potential therapeutic properties. This study investigates the herb's water extract's capacity to interfere with the interaction between the COVID-19 S1 Receptor Binding Domain (RBD) and the ACE2 receptor, a critical step in the virus's infection process.MethodsQuality standards for the Bergenia purpurascens extract were established to ensure consistency. The extract's efficacy was assessed using a Vero-E6 cell infection model to inhibit live virus infection of the COVID-19 XBB1.5 variant. Surface Plasmon Resonance (SPR) was employed to explore the mechanism of action. The extract's composition was further analyzed using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS), with active compounds identified through a combination of in silico screening and actual activity testing.ResultsThe water extract of Bergenia purpurascens demonstrated significant inhibitory activity against the COVID-19 XBB1.5 variant, with stability and high potency, reflected by an IC50 value of 0.037 mg/mL. The selectivity index for the antiviral effect is approximately 9. The extract's composition was predominantly Phenylpropanoids and Carbohydrates, accounting for over 60% of the total. Interestingly, a majority of the high-content compounds were inactive, while the low-content compounds, exemplified by Ellagic acid, showed synergistic activity. The extract's inhibitory mechanism was characterized as a non-specific inhibition of ACE2 with a steady-state binding affinity (KD) of 7.9 × 10−7 M.ConclusionsThe study concludes that the water extract of Bergenia purpurascens is a promising, cost-effective non-specific ACE2 inhibitor with potential applications in COVID-19 therapy. The identification of active compounds and the elucidation of its inhibitory mechanism provide a foundation for further research and development of this traditional medicinal herb in combating viral infections.
研究领域:
药理学
·
病毒学
·
分子生物学
✓ 已验证
DOI
高影响因子
Computational and Structural Biotechnology Journal
·
2023
·
IF 6
Boyu Pan,Senbiao Fang,Liangjiao Wang,Zhanyu Pan,Min Li,Liren Liu
The emergence of SARS-CoV-2-Spike mutants not only enhances viral infectivity but also lead to treatment failure. Gaining a comprehensive understanding of the molecular binding mode between the mutant SARS-CoV-2-Spike and human ACE2 receptor is crucial for therapeutic development against this virus. Building upon our previous predictions and verifications regarding heightened viral infectivity of six potential SARS-CoV-2-Spike mutants, this study aims to further investigate the potential disruption of the interaction between these mutants and ACE2 by quercetin, a Chinese herbal compound. Molecular docking and dynamics simulations results reveal that the binding sites of quercetin particularly enriched around a specific “cavity” at the interface of Spike/ACE2 complex, indicating a favorable region for quercetin to interfere with Spike/ACE2 interaction. Virus infection assay confirms that quercetin not only attenuates wild-type virus infectivity but also suppresses the infectivity of all six tested SARS-CoV-2-Spike mutants. Therefore, quercetin represents a promising therapeutic candidate against both wild-type and potential future variants of SARS-CoV-2 exhibiting high viral infectivity.
研究领域:
病毒学
·
药理学
·
计算生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL
·
2025
·
IF 42.5
Cheng-Bao Ma,Chen Liu,Young-Jun Park,Jingjing Tang,Jing Chen,Qing Xiong,Jimin Lee,Cameron Stewart,Daniel Asarnow,Jack Brown,M. Alejandra Tortorici,Xiao Yang,Ye-Hui Sun,Yuan-Mei Chen,Xiao Yu,Jun-Yu Si,Peng Liu,Fei Tong,Mei-Ling Huang,Jing Li,Zheng-Li Shi,Zengqin Deng,David Veesler,Huan Yan
The angiotensin-converting enzyme 2 (ACE2) receptor is shared by various coronaviruses with distinct receptor-binding domain (RBD) architectures, yet our understanding of these convergent acquisition events remains elusive. Here, we report that two bat MERS-related coronaviruses (MERSr-CoVs) infecting Pipistrellus nathusii ( P.nat )—MOW15-22 and PnNL2018B—use ACE2 as their receptor, with narrow ortholog specificity. Cryoelectron microscopy structures of the MOW15-22/PnNL2018B RBD-ACE2 complexes unveil an unexpected and entirely distinct binding mode, mapping >45 Å away from that of any other known ACE2-using coronaviruses. Functional profiling of ACE2 orthologs from 105 mammalian species led to the identification of host tropism determinants, including an ACE2 N432-glycosylation restricting viral recognition, and the design of a soluble P.nat ACE2 mutant with potent viral neutralizing activity. Our findings reveal convergent acquisition of ACE2 usage for merbecoviruses found in European bats, underscoring the extraordinary diversity of ACE2 recognition modes among coronaviruses and the promiscuity of this receptor.
研究领域:
病毒学
·
结构生物学
·
进化生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）