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
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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jingxuan Li,Feng Liu,Fushan Wu,Xiaoyue Su,Lihui Zhang,Xueru Zhao,Chao Shang,Lu Han,Yongxiang Zhang,Zhiyong Xiao,Wenxia Zhou
Viral respiratory infections are major human health concerns. The most striking epidemic disease, COVID-19 is still on going with the emergence of fast mutations and drug resistance of pathogens. A few polysaccharide macromolecules from traditional Chinese medicine (TCM) have been found to have direct anti-SARS-CoV-2 activity but the mechanism remains unclear. In this study, we evaluated the entry inhibition effect of Lycium barbarum polysaccharides (LBP) in vitro and in vivo. We found LBP effectively suppressed multiple SARS-CoV-2 variants entry and protected K18-hACE2 mice from invasion with Omicron pseudovirus (PsV). Moreover, we found LBP interfered with early entry events during infection in time-of-addition (TOA) assay and SEM observation. Further surface plasmon resonance (SPR) study revealed the dual binding of LBP with Spike protein and ACE2, which resulted in the disruption of Spike-ACE2 interaction and subsequently triggered membrane fusion . Therefore, LBP may act as broad-spectrum inhibitors of virus entry and nasal mucosal protective agent against newly emerging respiratory viruses , especially SARS-CoV-2.
研究领域:
医学
·
分子生物学
·
病毒学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2021
·Vol. 33
·期 34
·2101707
·
IF 30.849
Min Li,Sanpeng Li,Yixuan Huang,Haixia Chen,Songya Zhang,Zhicheng Zhang,Weigang Wu,Xiaobin Zeng,Boping Zhou,Bin Li
The transfer of foreign synthetic messenger RNA (mRNA) into cells is essential for mRNA-based protein-replacement therapies. Prophylactic mRNA COVID-19 vaccines commonly utilize nanotechnology to deliver mRNA encoding SARS-CoV-2 vaccine antigens, thereby triggering the body's immune response and preventing infections. In this study, a new combinatorial library of symmetric lipid-like compounds is constructed, and among which a lead compound is selected to prepare lipid-like nanoassemblies (LLNs) for intracellular delivery of mRNA. After multiround optimization, the mRNA formulated into core–shell-structured LLNs exhibits more than three orders of magnitude higher resistance to serum than the unprotected mRNA, and leads to sustained and high-level protein expression in mammalian cells. A single intravenous injection of LLNs into mice achieves over 95% mRNA translation in the spleen, without causing significant hematological and histological changes. Delivery of in-vitro-transcribed mRNA that encodes high-affinity truncated ACE2 variants (tACE2v mRNA) through LLNs induces elevated expression and secretion of tACE2v decoys, which is able to effectively block the binding of the receptor-binding domain of the SARS-CoV-2 to the human ACE2 receptor. The robust neutralization activity in vitro suggests that intracellular delivery of mRNA encoding ACE2 receptor mimics via LLNs may represent a potential intervention strategy for COVID-19.
研究领域:
纳米技术
·
分子生物学
·
药学
·
病毒学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 13
·3022
·
IF 4.2
Yuping Wei,Ziyang Liu,Man Zhang,Xingyan Zhu,Qiuhong Niu
Considering the high evolutionary rate and great harmfulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is imperative to develop new pharmacological antagonists. Human angiotensin-converting enzyme-2 (ACE2) functions as a primary receptor for the spike protein (S protein) of SARS-CoV-2. Thus, a novel functional peptide, KYPAY (K5), with a boomerang structure, was developed to inhibit the interaction between ACE2 and the S protein by attaching to the ACE2 ligand-binding domain (LBD). The inhibition property of K5 was evaluated via molecular simulations, cell experiments, and adsorption kinetics analysis. The molecular simulations showed that K5 had a high affinity for ACE2 but a low affinity for the cell membrane. The umbrella sampling (US) simulations revealed a significant enhancement in the binding potential of this functional peptide to ACE2. The fluorescence microscopy and cytotoxicity experiments showed that K5 effectively prevented the interaction between ACE2 and the S protein without causing any noticeable harm to cells. Further flow cytometry research indicated that K5 successfully hindered the interaction between ACE2 and the S protein, resulting in 78% inhibition at a concentration of 100 μM. This work offers an innovative perspective on the development of functional peptides for the prevention and therapy of SARS-CoV-2.
研究领域:
药理学
·
病毒学
·
分子生物学
·
生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Infectious Diseases and Therapy
·
2021
·Vol. 10
·期 1
·483-494
·
IF 5.322
Xu Huan,Liu Bing,Xiao Zhen,Zhou Meiling,Ge Lin,Jia Fan,Liu Yanling,Jin Hongshan,Zhu Xiuliang,Gao Jian,Akhtar Javed,Xiang Bai,Tan Ke,Wang Guanyu
Introduction Since December 2019, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic in China and worldwide. New drugs for the treatment of COVID-19 are in urgent need. Considering the long development time for new drugs, the identification of promising inhibitors from FDA-approved drugs is an imperative and valuable strategy. Recent studies have shown that the S1 and S2 subunits of the spike protein of SARS-CoV-2 utilize human angiotensin-converting enzyme 2 (hACE2) as the receptor to infect human cells. Methods We combined molecular docking and surface plasmon resonance (SPR) to identify potential inhibitors for ACE2 from available commercial medicines. We also designed coronavirus pseudoparticles that contain the spike protein assembled onto green fluorescent protein or luciferase reporter gene-carrying vesicular stomatitis virus core particles. Results We found that thymoquinone, a phytochemical compound obtained from the plant Nigella sativa , is a potential drug candidate. SPR analysis confirmed the binding of thymoquinone to ACE2. We found that thymoquinone can inhibit SARS-CoV-2, SARS-CoV, and NL63 pseudoparticles infecting HEK293-ACE2 cells, with half-maximal inhibitory concentrations of 4.999, 7.598, and 6.019 μM, respectively. The SARS-CoV-2 pseudoparticle inhibition had half-maximal cytotoxic concentration of 35.100 μM and selection index = 7.020. Conclusion Thymoquinone is a potential broad-spectrum inhibitor for the treatment of coronavirus infections.
研究领域:
药理学
·
病毒学
·
分子生物学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2023
·
IF 4.4
Yansheng Liu,Zhenle Qin,Xiaobo Jia,Jin Zhou,Hongli Li,Xiaohong Wang,Yating Chen,Junpeng Deng,Zhicheng Jin,Guofu Wang
The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a great disaster to the economy and human society. Nowadays, SARS-CoV-2 is fading away from people’s memory but it still exists around us. PCR plays an important role in detecting SARS-CoV-2 but it requires a long detecting time, equipped laboratory, and professional operators. In comparison with polymerase chain reaction (PCR), surface-enhanced Raman scattering (SERS) is a promising method for detecting SARS-CoV-2 due to its fast, easily operated, and high-sensitivity properties. In this study, the monolayer Ag nanoparticles (MAgNPs) covered with single-layer graphene (SLG) are applied as a SERS substrate. The angiotensin converting enzyme 2 (ACE2) is selected as a bio-probes that can specifically bind to the SARS-CoV-2 S protein. The SERS-based biosensor is formed by ACE2 functionalized SLG/MAgNPs and the LODs of detecting SARS-CoV-2 S protein in phosphate-buffered saline (PBS) and in pharyngeal swabs solution (PSS) are 0.1 fg mL −1 and 10 fg mL −1 , respectively. This biosensor provides a way of directly detecting SARS-CoV-2 S protein with high sensitivity and specificity. It illustrates a practical potential in the rapid detection of the SARS-CoV-2 virus.
研究领域:
生物传感器
·
医学检测
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Peptide Research and Therapeutics
·
2024
·Vol. 30
·期 5
·1-13
·
IF 2
Liu Ziyang,Wei Yuping,Zhang Man,Zhu Xingyan,Liu Kun
Angiotensin-converting enzyme-2 (ACE2) is a important cell surface receptor of SARS-CoV-2 S protein. The initial stage of SARS-COV-2 cell infection involves the binding of the S protein to ACE2. Hence, this work presents an innovative strategy to designing ACE2-based peptide inhibitors by considering the surface property and morphology of the S protein RBD. The aim is to develop a short peptide inhibitor that can effectively inhibit S protein-ACE2 interaction Through computational analysis and molecular simulation, the surface properties and morphology of S protein receptor-binding structural domain (RBD) were investigated, while the key residues of ACE2 ligand-binding structural domain (LBD) were identified based on their contributions and non-covalent interactions. Then, peptide inhibitors, consisting of ACE2 key residues, were developed by fitting to the surface characteristics and topographical features of the S protein RBD. Molecular simulation showed that two novel short peptides, IEPFF (I5) and WIEPFF (W6) had high affinity for S protein RBD but a low affinity for the cell membrane. Cellular adsorption studies demonstrated that both I5 and W6 effectively blocked ACE2-S protein binding without significant cytotoxicity. Flow cytometry analysis revealed that both I5 and W6 effectively inhibited S protein binding to the ACE2, resulting in a significant reduction (75 and 79%, respectively) in fluorescence intensity after 30 min of incubation at a concentration of 200 μM. Both I5 and W6 were excellent potential anti SARS-COV-2 drugs. This work provides an innovative perspective for the development of functional peptides for the prevention and management of SARS-COV-2.
研究领域:
生物化学
·
分子生物学
·
病毒学
·
药学
·
计算生物学
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Zhenle Qin,Yansheng Liu,Xiaobo Jia,Jin Zhou,Hongli Li,Xiaohong Wang,Shaohui Zhang,Haixin Chang,Guofu Wang
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in widespread disease transmission, challenging the stability of global healthcare systems. Surface-enhanced Raman scattering (SERS) as an easy operation, fast, and low-cost technology illustrates a good potential in detecting SARS-CoV-2. In the study, one-step fabrication of gold-silver alloy nanoparticles (AuAgNPs) with adjustable metal proportions and diameters is employed as SERS substrates. The angiotensin-converting enzyme 2 (ACE2) functionalized AuAgNPs are applied as sensor surfaces to detect SARS-CoV-2 S protein. By optimizing the SERS substrates, ACE2/Au 35 Ag 65 NPs illustrate higher performance in detecting the SARS-CoV-2 S protein with a limit of detection (LOD) of 10 fg/mL in both phosphate-buffered saline (PBS) and pharyngeal swabs solution (PSS). It also provides excellent reproducibility with a relative standard deviation (RSD) of 7.7 % and 7.9 %, respectively. This easily preparable and highly reproducible SERS substrate has good potential in the practical application of detecting SARS-CoV-2.
研究领域:
生物医学
·
纳米技术
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2022
·Vol. 11
·期 18
·2865
·
IF 5.561
Jinghe Sun,Shuang Song,Chunqing Ai,Beiwei Zhu,Jingfeng Yang
Sulfate polysaccharides, such as heparin sulfate, have been found to have inhibitory activity against SARS-CoV-2. An abalone polysaccharide, AGSP, was deeply sulfate modified using the chlorosulfonic acid/pyridine method, yielding S-AGSP. AGSP and S-AGSP inhibitions of SARS-CoV-2 infection of Vero E6 cells were tested in vitro. The interference of AGSP or S-AGSP on the binding interaction between the SARS-CoV-2 spike protein and angiotensin-converting enzyme was tested using a biolayer interferometry assay. Results showed that S-AGSP, above a concentration of 1.87 µg/mL, significantly inhibited SARS-CoV-2 infection of Vero E6 cells. Compared with AGSP, S-AGSP obviously weakened the affinity between the SARS-CoV-2 spike protein and ACE2. The polysaccharide’s sulfate content played a vital role in influencing the binding affinity of spike protein to ACE2. Therefore, S-AGSP has potential as a COVID-19 competitive inhibitor as well as a candidate to be repurposed as a prophylactic COVID-19 therapeutic.Keywords:sulfated;polysaccharide;SARS-CoV-2;biolayer interferometry;ACE2
研究领域:
病毒学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Bing Zhao,Chan-Ru Xiong,Yao Liu,Qing-Cai Yu,Xing Chen
The outbreak of novel coronavirus pneumonia (COVID-19) in 2019 has garnered widespread attention. The virus exhibits high contagiousness, and in certain cases, it can lead to recurrent infections. Therefore, it is imperative to develop portable, sensitive, and accurate sensors to promptly detect infected individuals, control the virus's transmission, and determine suitable treatment strategies. In this study, we proposed a magnetically-assisted method employing CFO@CS-Au MNP as the substrate material, which was functionalized with human angiotensin-converting enzyme (ACE2) for efficient capture of SARS-CoV-2 spike protein in solution. Subsequently, the captured protein was sensitively detected through differential pulse voltammetry (DPV) electrical analysis. The linear detection range of the labeled GCE/MNP/GA/ACE2/BSA electrochemical sensor is from 1 pg/mL to 10 μg/mL, with a minimum detection limit of 0.15 pg/mL. Furthermore, the fabricated GCE/MNP/GA/ACE2/BSA sensor achieved satisfactory recoveries of SARS-CoV-2 spike protein in saliva and nasal swab samples within 10 min. These results indicate that this magnetically-assisted biosensor has established a solid foundation for the swift on-site detection of COVID-19.
研究领域:
医学诊断
·
生物传感技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Tong Zhao,Luying Xu,Wenjie Huang,Cong Wang,Huanhuan Wang,Mengyue Du,Chang Yao,Yanlei Xu
Background Breast cancer progression depends on abnormal angiogenesis, driven by VEGF/VEGFR2/ERK and inhibited by Angiotensin-Converting Enzyme 2 (ACE2). Chrysophanol (CHR) shows anti-breast cancer efficacy, but its mechanism is unclear. Methods Anti-tumor effects were assessed by measuring tumor volume, H&E staining, Ki67 immunohistochemistry, MTT, scratch wound, and Transwell assays. Anti-angiogenic effects were evaluated via Platelet Endothelial Cell Adhesion Molecule-1 (CD31) immunohistochemistry, CAM assay and Western blot (WB) of VEGF-A, Hypoxia-Inducible Factor 1-α (HIF-1α), and VEGFA/VEGFR2/ERK pathway proteins. The mechanism was explored by WB analysis of ACE2 expression/ubiquitination, validated by siRNA knockdown and CETSA for binding site identification. Results Both in vivo and in vitro experiments demonstrated that chrysophanol reduces tumor cell viability, suppresses tumor cell growth, migration, and invasion, inhibiting the progression of breast cancer. Given the critical role of angiogenesis in tumor development, further studies revealed that chrysophanol downregulates the expression of proteins such as HIF-1α and Vascular Endothelial Growth Factor A (VEGFA), indicating that it inhibits tumor angiogenesis by suppressing the VEGFA/VEGFR2/ERK signaling pathway. Since prior evidence suggests that this pathway acts downstream of ACE2, we examined ACE2 protein levels and found that chrysophanol reduces ACE2 ubiquitination, and enhances its stability and expression. This upregulation of ACE2 further inhibits the downstream VEGFA/VEGFR2/ERK pathway. Moreover, molecular docking confirmed that chrysophanol binds specifically to the active pocket 888 of the ACE2 protein. All the observed inhibitory effects on breast cancer were dose-dependent. Conclusion All the data shows that chrysophanol can reduce tumor angiogenesis and alleviate breast cancer growth. It also confirms that chrysophanol can promote ACE2 expression to inhibit the VEGFa/VEGFR2/ERK signaling pathway, thereby suppressing breast cancer development.
✓ 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）