Affinity ultrafiltration and UPLC-HR-Orbitrap-MS based screening of thrombin-targeted small molecules with anticoagulation activity from Poecilobdella manillensis

Huang, Qiuyang; Tang, Jianyuan; Chai, Xiaoxin; Ren, Wei; Wang, Jiabo; Gan, Qichao; Shi, Jingyan; Wang, Manyuan; Yang, Sijin; Liu, Jingfang; Ma, Li

doi:10.1016/j.jchromb.2021.122822

Cited by 13 publications

(5 citation statements)

References 49 publications

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“…Centrifugal ultrafiltration utilizes centrifugal force and a semipermeable membrane to retain suspended solids and high molecular weight solutes, while allowing liquid and low molecular weight solutes to penetrate the membrane based on the pore size of the membrane. Due to its simple operation, high speed, and high reliability, centrifugal ultrafiltration has become a useful technology for screening active compounds from natural complex matrices 27,29–31 . However, there are currently no reported screening methods for directly identifying virus‐targeted compounds from complex matrices.…”

Section: Introductionmentioning

confidence: 99%

“…Due to its simple operation, high speed, and high reliability, centrifugal ultrafiltration has become a useful technology for screening active compounds from natural complex matrices. 27,[29][30][31] However, there are currently no reported screening methods for directly identifying virustargeted compounds from complex matrices. Therefore, it is necessary to further develop a simple, rapid and effective screening method to specifically screen active compounds targeting viruses from complex matrices such as HMs.…”

Section: Introductionmentioning

confidence: 99%

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Development of a virus‐based affinity ultrafiltration method for screening virus‐surface‐protein‐targeted compounds from complex matrixes: Herbal medicines as a case study

Li,

Liu

et al. 2024

Journal of Medical Virology

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Herbal medicines (HMs) are one of the main sources for the development of lead antiviral compounds. However, due to the complex composition of HMs, the screening of active compounds within these is inefficient and requires a significant time investment. We report a novel and efficient virus‐based screening method for antiviral active compounds in HMs. This method involves the centrifugal ultrafiltration of viruses, known as the virus‐based affinity ultrafiltration method (VAUM). This method is suitable to identify virus specific active compounds from complex matrices such as HMs. The effectiveness of the VAUM was evaluated using influenza A virus (IAV) H1N1. Using this method, four compounds that bind to the surface protein of H1N1 were identified from dried fruits of Terminalia chebula (TC). Through competitive inhibition assays, the influenza surface protein, neuraminidase (NA), was identified as the target protein of these four TC‐derived compounds. Three compounds were identified by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS), and their anti‐H1N1 activities were verified by examining the cytopathic effect (CPE) and by performing a virus yield reduction assay. Further mechanistic studies demonstrated that these three compounds directly bind to NA and inhibit its activity. In summary, we describe here a VAUM that we designed, one that can be used to accurately screen antiviral active compounds in HMs and also help improve the efficiency of screening antiviral drugs found in natural products.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a virus‐based affinity ultrafiltration method for screening virus‐surface‐protein‐targeted compounds from complex matrixes: Herbal medicines as a case study

Li,

Liu

et al. 2024

Journal of Medical Virology

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“…Then, the ligand-enzyme complexes are denatured and the released ligands are analyzed by LC-MS/MS [17]. Compared with the traditional method, UF-MS has the advantages of small sample size, simple operation, and strong targeting [17,18].…”

Section: Introductionmentioning

confidence: 99%

Discovery of the potential neuraminidase inhibitors from Polygonum cuspidatum by ultrafiltration combined with mass spectrometry guided by molecular docking

Wang

Chen

Sun

et al. 2023

J of Separation Science

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Neuraminidase is an important target in the treatment of the influenza A virus.Screening natural neuraminidase inhibitors from medicinal plants is crucial for drug research. This study proposed a rapid strategy for identifying neuraminidase inhibitors from different crude extracts (Polygonum cuspidatum, Cortex Fraxini, and Herba Siegesbeckiae) using ultrafiltration combined with mass spectrometry guided by molecular docking. Firstly, the main component library of the three herbs was established, followed by molecular docking between the components and neuraminidase. Only the crude extracts with numbers of potential neuraminidase inhibitors identified by molecular docking were selected for ultrafiltration. This guided approach reduced experimental blindness and improved efficiency. The results of molecular docking indicated that the compounds in Polygonum cuspidatum demonstrated good binding affinity with neuraminidase. Subsequently, ultrafiltration-mass spectrometry was employed to screen for neuraminidase inhibitors in Polygonum cuspidatum. A total of five compounds were fished out, and they were identified as trans-polydatin, cispolydatin, emodin-1-O-β-D-glucoside, emodin-8-O-β-D-glucoside, and emodin.The enzyme inhibitory assay showed that they all had neuraminidase inhibitory effects. In addition, the key residues of the interaction between neuraminidase and fished compounds were predicted. In all, this study could provide a strategy for the rapid screening of the potential enzyme inhibitors from medicinal herbs.

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“…The salivary glands of hematophagous leeches secrete an abundance of anticoagulant substances [25][26][27][28][29], and recently several novel antimicrobial peptides have been identified from these leeches such as Hirudo nipponica Whitman and Hirudo medicinalis [30][31][32]. H. manillensis is the most commonly available leech from the Chinese commercial leech market, and we and other researchers have identified a variety of anticoagulant peptides, analgesic peptides, and other active molecules from the salivary gland of H. manillensis [33][34][35][36][37]. However, no antimicrobial peptides from H. manillensis have been reported.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of RK22, a Novel Antimicrobial Peptide from Hirudinaria manillensis against Methicillin Resistant Staphylococcus aureus

Lu,

Yang,

Zhou

et al. 2023

IJMS

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Staphylococcus aureus (S. aureus) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus potentially aggravating infectious diseases. Recently, we and other researchers identified that a higher level of LL-37, one endogenous antimicrobial peptide with a significant killing effect on S. aureus infection, resulted in thrombosis formation through the induction of platelet activation and potentiation of the coagulation factor enzymatic activity. In the current study, we identified a novel antimicrobial peptide (RK22) from the salivary gland transcriptome of Hirudinaria manillensis (H. manillensis) through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against S. aureus, including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 μg/mL. The RK22 peptide rapidly killed S. aureus by inhibiting biofilm formation and promoting biofilm eradication, with good plasma stability, negligible cytotoxicity, minimal hemolytic activity, and no significant promotion of the coagulation system. Notably, administration of RK22 significantly inhibited S. aureus infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against S. aureus infection.

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Affinity ultrafiltration and UPLC-HR-Orbitrap-MS based screening of thrombin-targeted small molecules with anticoagulation activity from Poecilobdella manillensis

Cited by 13 publications

References 49 publications

Development of a virus‐based affinity ultrafiltration method for screening virus‐surface‐protein‐targeted compounds from complex matrixes: Herbal medicines as a case study

Development of a virus‐based affinity ultrafiltration method for screening virus‐surface‐protein‐targeted compounds from complex matrixes: Herbal medicines as a case study

Discovery of the potential neuraminidase inhibitors from Polygonum cuspidatum by ultrafiltration combined with mass spectrometry guided by molecular docking

Identification and Characterization of RK22, a Novel Antimicrobial Peptide from Hirudinaria manillensis against Methicillin Resistant Staphylococcus aureus

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