Current computer-aided drug design最新文献

{"title":"Chemical Synthesis, Biological Evaluation, and Cheminformatics Analysis of a Group of Chlorinated Diaryl Sulfonamides: Promising Inhibitors of Cholesteryl Ester Transfer Protein.","authors":"Reema Abu Khalaf, Ala'a Lafi, Rima Hajjo, Mahmoud A Al-Sha'er","doi":"10.2174/0115734099292078240218095540","DOIUrl":"https://doi.org/10.2174/0115734099292078240218095540","url":null,"abstract":"<p><strong>Background: </strong>Hyperlipidemia is characterized by an abnormally elevated serum cholesterol, triglycerides, or both. The relationship between an elevated level of LDL and cardiovascular diseases is well-established. Cholesteryl ester transfer protein (CETP) is an enzyme that moves cholesterol esters and triglycerides between LDL, VLDL, and HDL. CETP inhibition leads to a reduction in cardiovascular disease by raising HDL and minimizing LDL.</p><p><strong>Objective: </strong>This study synthesized ten meta-chlorinated benzene sulfonamides 6a-6j and explored their structure-activity relationship.</p><p><strong>Methods: </strong>The synthesized molecules were characterized using 1H-NMR, 13C-NMR, IR, and HR-MS. Moreover, cheminformatics analyses included pharmacophore mapping, LibDock studies, and cheminformatics characterization using 2-dimensional (2D) molecular descriptors and principal component analysis.</p><p><strong>Results: </strong>Based on in vitro functional CETP assays, compounds 6e, 6i, and 6j demonstrated the strongest inhibitory activities against CETP, reaching 100% inhibition. The inhibitory activity of compounds 6a-6d and 6f-6h ranged from 47.5% to 96.5% at 10 μM concentration. Pharmacophore mapping results suggested CETP inhibitory action, while the docking scores and calculated binding energies predicted favoring binding at the CETP active site. Best-scoring docking poses predicted critical hydrophobic features corresponding to key interactions with His232 and Cys13. Cheminformatics analysis using 2D molecular descriptors indicated that the synthesized compounds span various physicochemical properties and drug-likeness.</p><p><strong>Conclusion: </strong>It was found that a chloro moiety at the ortho-position, or a nitro group at the meta and para-positions, improves the CETP inhibitory activity of synthesized analogs. Computational studies suggest the formation of stable ligand-protein complexes between compounds 6a- 6j and CETP.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Compound Dioscin Targeting Multiple Cancer Pathways through its High Affinity Binding to B Cell Lymphoma-2.","authors":"Shweta Gulia, Prakash Chandra, Asmita Das","doi":"10.2174/0115734099279130231211053542","DOIUrl":"https://doi.org/10.2174/0115734099279130231211053542","url":null,"abstract":"<p><strong>Objective: </strong>The study aimed to explore the crucial genes involved in cancer-related biological processes, including EMT, autophagy, apoptosis, anoikis, and metastasis. It also sought to identify common genes among the pathways linked to these biological processes, determine the level of Bcl-2 expression in various types of cancers, and find a potent inhibitor of Bcl-2 among natural compounds.</p><p><strong>Methods: </strong>Common genes involved in the pathways related to EMT, autophagy, apoptosis, anoikis, and metastasis were explored, and the level of the most frequently overexpressed gene that was Bcl-2, in various types of cancers was analyzed by gene expression analysis. A set of 102 natural compounds was sorted according to their docking scores using molecular docking and filtering. The top-ranked molecule was chosen for additional molecular dynamics (MD) simulation for 100 ns. Differential gene expression analysis was performed for Dioscin using GEO2R.</p><p><strong>Results: </strong>The study identified four common genes, Bcl-2, Bax, BIRC3, and CHUK, among the pathways linked to EMT, autophagy, apoptosis, anoikis, and metastasis. Bcl-2 was highly overexpressed in many cancers, including Acute Myeloid Leukemia, Diffuse large B cell lymphoma, and Thymoma. The Dioscin structure in the Bcl-2 binding site received the highest docking score and the most relevant interactions. Dioscin's determined binding free energy by MM/GBSA was -52.21 kcal/mol, while the same calculated by MM/PBSA was -9.18 kcal/mol. A p-value of less than 0.05 was used to determine the statistical significance of the analysis performed using GEO2R. It was observed that Dioscin downregulates Bcl-2, BIRC3, and CHUK and upregulates the pro-apoptotic protein Bax.</p><p><strong>Conclusion: </strong>The study concluded that Dioscin has the potential to act as a protein inhibitor, with a noteworthy value of binding free energy and relevant interactions with the Bcl-2 binding site. Dioscin might be a good alternative for targeting multiple cancer pathways through a single target.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139907115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WSHNN: A Weakly Supervised Hybrid Neural Network for the Identification of DNA-Protein Binding Sites.","authors":"Wenzheng Bao, Baitong Chen, Yue Zhang","doi":"10.2174/0115734099277249240129114123","DOIUrl":"https://doi.org/10.2174/0115734099277249240129114123","url":null,"abstract":"<p><strong>Introduction: </strong>Transcription factors are vital biological components that control gene expression, and their primary biological function is to recognize DNA sequences. As related research continues, it was found that the specificity of DNA-protein binding has a significant role in gene expression, regulation, and especially gene therapy. Convolutional Neural Networks (CNNs) have become increasingly popular for predicting DNa-protein-specific binding sites, but their accuracy in prediction needs to be improved.</p><p><strong>Methods: </strong>We proposed a framework for combining multi-Instance Learning (MIL) and a hybrid neural network named WSHNN. First, we utilized sliding windows to split the DNA sequences into multiple overlapping instances, each instance containing multiple bags. Then, the instances were encoded using a K-mer encoding. Afterward, the scores of all instances in the same bag were calculated separately by a hybrid neural network.</p><p><strong>Results: </strong>Finally, a fully connected network was utilized as the final prediction for that bag. The framework could achieve the performances of 90.73% in Pre, 82.77% in Recall, 87.17% in Acc, 0.8657 in F1-score, and 0.7462 in MCC, respectively. In addition, we discussed the performance of K-mer encoding. Compared with other art-of-the-state efforts, the model has better performance with sequence information.</p><p><strong>Conclusion: </strong>From the experimental results, it can be concluded that Bi-directional Long-ShortTerm Memory (Bi-LSTM) can better capture the long-sequence relationships between DNA sequences (the code and data can be visited at https://github.com/baowz12345/Weak_ Super_Network).</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the Mechanisms of Cinnamic Acid Treating Diabetic Nephropathy Based on Network Pharmacology, Molecular Docking, and Experimental Validation.","authors":"Limiao Dai, Yang He, Siqiang Zheng, Jiyu Tang, Lanjun Fu, Li Zhao","doi":"10.2174/0115734099286283240130115111","DOIUrl":"https://doi.org/10.2174/0115734099286283240130115111","url":null,"abstract":"<p><strong>Background: </strong>Cinnamic acid (Cinn) is a phenolic acid of Cinnamomum cassia (L.) J. Presl. that can ameliorate diabetic nephropathy (DN). However, comprehensive therapeutic targets and underlying mechanisms for Cinn against DN are limited.</p><p><strong>Objective: </strong>In this study, a network pharmacology approach and in vivo experiments were adopted to predict the pharmacological effects and mechanisms of Cinn in DN therapy.</p><p><strong>Methods: </strong>The nephroprotective effect of Cinn on DN was investigated by a streptozotocininduced diabetes mellitus (DM) mouse model. The protein-protein interaction network of Cinn against DN was established by a network pharmacology approach. The core targets were then identified and subjected to molecular docking with Cinn.</p><p><strong>Results: </strong>Cinn treatment effectively restored body weight, ameliorated hyperglycemia, and reduced kidney dysfunction markers in DM mice, also demonstrating a reduction in tissue injury. Network pharmacology analysis identified 298 DN-Cinn co-target genes involved in various biological processes and pathways. Seventeen core targets were identified, eight of which showed significant differential expression in the DN and healthy control groups. Molecular docking analysis revealed a strong interaction between Cinn and PTEN. Cinn treatment downregulated the PTEN protein expression in DM mice.</p><p><strong>Conclusion: </strong>This study revealed the multi-target and multi-pathway characteristics of Cinn against DN. Cinn improved renal pathological damage of DN, which was related to the downregulation of PTEN.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An In silico Study on B-cell Epitope Mapping of Acinetobacter baumannii Outer Membrane Protein K.","authors":"Hana Heidarinia, Keyghobad Ghadiri, Fatemeh Nemati Zargaran, Roya Chegene Lorestani, Mosayeb Rostamian","doi":"10.2174/0115734099281401240118054834","DOIUrl":"https://doi.org/10.2174/0115734099281401240118054834","url":null,"abstract":"<p><strong>Background: </strong>Acinetobacter baumannii is one of the main causes of nosocomial infections. No vaccine has yet been licensed for use in humans, and efforts are still ongoing.</p><p><strong>Objective: </strong>In the present study, we have predicted the B-cell epitopes of A. baumannii's outer membrane protein K (OMPK) by using epitope prediction algorithms as possible vaccine candidates for future studies.</p><p><strong>Methods: </strong>The linear B-cell epitopes were predicted by seven different prediction tools. The 3D structure of OMPK was modeled and used for discontinuous epitope prediction by ElliPro and DiscoTope 2.0 tools. The final linear epitopes and the discontinuous epitope segments were checked for potential allergenicity, toxicity, human similarity, and experimental records. The structure and physicochemical features of the final epitopic peptide were assessed by numerous bioinformatics tools.</p><p><strong>Results: </strong>Many B-cell epitopes were detected that could be assessed for possible antigenicity and immunogenicity. Also, an epitopic 22-mer region (peptide) of OMPK was found that contained both linear and discontinuous B-cell epitopes. This epitopic peptide has been found to possess appropriate physicochemical and structural properties to be an A. baumannii vaccine candidate.</p><p><strong>Conclusion: </strong>Altogether, here, the high immunogenic B-cell epitopes of OMPK have been identified, and a high immunogenic 22-mer peptide as an A. baumannii vaccine candidate has been introduced. The in vitro/in vivo studies of this peptide are recommended to decide its real efficacy and efficiency.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Study of Antimicrobial Peptides for Promising Therapeutic Applications Against Methicillin-resistant Staphylococcus Aureus.","authors":"Priyanka Sinoliya, Pooran Singh Solanki, Ravi Ranjan Kumar Niraj, Vinay Sharma","doi":"10.2174/0115734099285473240101111303","DOIUrl":"https://doi.org/10.2174/0115734099285473240101111303","url":null,"abstract":"<p><strong>Background: </strong>Methicillin-resistant Staphylococcus aureus (MRSA) is a causative agent for multiple drug-resistant diseases and is a prime health concern. Currently, antibiotics like vancomycin, daptomycin, fluoroquinolones, linezolid, fifth-generation cephalosporin and others are available in the market for the treatment of MRSA infection.</p><p><strong>Methods: </strong>With the increasing prevalence of drug-resistant cases, researchers are actively investigating alternative strategies to combat MRSA, including the exploration of peptide therapeutics. This study employed computational methods to prospect for potential Antimicrobial Peptides (AMPs).</p><p><strong>Results: </strong>A total of One hundred and fifty antimicrobial peptides were explored based on physicochemical properties. The results showed that Clavanin B was the most appropriate candidate. Molecular Docking and Molecular Dynamics Simulation results showed the protein-peptide interaction of the MRSA target proteins, Penicillin Binding Protein 2a and Panton-Valentine Leukocidin Toxin, with the Antimicrobial Peptide Clavanin B.</p><p><strong>Conclusion: </strong>Currently, the antimicrobial peptide database highlights Clavanin B's role as an anti-HIV peptide. Moreover, this investigation proposes Clavanin B as a viable repurposed drug for treating MRSA, underscoring its potential deployment in the management of MRSA infections.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanism Analysis of the Effect of Hederagenin Combined with L-OHP on Chemosensitivity of AGS/L-OHP Based on Network Pharmacology.","authors":"Hongyue Tang, Chao Wang, Chenhao Xing, Guoxin Liang, Chang Guo, Xin Liu, YanJie Li, Mingming Zhang","doi":"10.2174/0115734099270389240104050955","DOIUrl":"https://doi.org/10.2174/0115734099270389240104050955","url":null,"abstract":"<p><strong>Aims and objectives: </strong>This study aimed to evaluate the pharmacological mechanism of Hederagenin (HD) combined with oxaliplatin (L-OHP) in treating gastric cancer (GC) through network pharmacology combined with experimental verification.</p><p><strong>Material and methods: </strong>Network pharmacology methods were used to screen potential targets for HD, L-OHP, and GC-related targets from public databases, and the intersection of the three gene sets was taken. Cross genes were analyzed through protein-protein interaction (PPI) networks to predict core targets, and related pathways were predicted through GO and KEGG enrichment analysis. The experimental results were verified by the in vitro experiments. HD was applied on AGS/L-OHP cells, and then cellular chemosensitivity and the expressions of P-gp, Survivin, Bcl-2, p-Akt, and p-PI3K genes were detected. Wound assay and Transwell Chamber assay were employed to detect the effect of HD on AGS/L-OHP cells. Nude mice xenograft models transfected using AGS/L-OHP cells were also treated with HD in order to verify the results. The size and weight of the tumor, as well as the expressions of P-gp, Survivin, Bcl-2, p- Akt and p-PI3K genes, were also measured.</p><p><strong>Results: </strong>KEGG analysis showed that the anti-gastric cancer effect of HD was mediated mainly by PI3K-Akt signaling pathways. The PI3K-Akt signaling pathway containing more enriched genes may play a greater role in anti-gastric cancer. It was observed that for AGS/L-OHP cells jointly treated with HD and L-OHP, their activity, migration and invasion were significantly lower than those treated only using HD or L-OHP group. Moreover, expressions of p-Akt, p- PI3K, Bcl-2, P-gp, and Survivin for the HD+L-OHP group decreased significantly. Results of the in vivo experiments showed that the sizes and weights of tumors in the HD+L-OHP group were the lowest compared to the HD group and L-OHP group.</p><p><strong>Conclusion: </strong>Our findings suggest that HD may reduce the resistance of AGS/L-OHP cells to LOHP by regulating the PI3K/Akt signaling pathway.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluorinated Diaryl Sulfonamides: Molecular Modeling, Synthesis, and <i>In Vitro</i> Validation as New CETP Inhibitors.","authors":"Reema Abu Khalaf, Azhar Shalluf, Maha Habash","doi":"10.2174/0115734099268407230927113905","DOIUrl":"10.2174/0115734099268407230927113905","url":null,"abstract":"<p><strong>Background: </strong>Hyperlipidemia, a cardiovascular disease risk factor, is characterized by a rise in low-density lipoprotein (LDL), triglycerides and total cholesterol, and a decrease in high-density lipoprotein (HDL). Cholesteryl ester transfer protein (CETP) enables the transfer of cholesteryl ester from HDL to LDL and very low-density lipoprotein.</p><p><strong>Objectives: </strong>CETP inhibition is a promising approach to prevent and treat cardiovascular diseases. By inhibiting lipid transport activity, it increases HDL levels and decreases LDL levels.</p><p><strong>Materials and method: </strong>Herein, diaryl sulfonamides 6a-6g and 7a-7g were prepared, and the structure of these compounds was fully determined using different spectroscopic techniques.</p><p><strong>Results: </strong>These compounds underwent biological evaluation <i>in vitro</i> and showed different inhibitory activities against CETP; 100% inhibitory activity was observed for compounds 7a-7g, while activities of compounds 6a-6g ranged up to 42.6% at 10 μM concentration. Pharmacophore mapping agreed with the bioassay results where the four aromatic ring compounds 7a-7g possessed higher fit values against Hypo4/8 and the shape-complemented Hypo4/8 in comparison to compounds 6a-6g.</p><p><strong>Conclusion: </strong>Docking of the synthesized compounds using libdock and ligandfit engines revealed that compounds 7a-7g formed п-п stacking and hydrophobic interactions with the binding pocket, while compounds 6a-6g missed these hydrophobic interactions with amino acids Leu206, Phe265, and Phe263.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"987-997"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In-silico</i> Investigation of Ginseng Phytoconstituents as Novel Therapeutics Against MAO-A.","authors":"Diksha Choudhary, Rajwinder Kaur, Nidhi Rani, Thakur Gurjeet Singh, Bhupinder Kumar","doi":"10.2174/0115734099266270230925090023","DOIUrl":"10.2174/0115734099266270230925090023","url":null,"abstract":"<p><strong>Background: </strong>Ginseng (<i>Panax ginseng</i>) is a herb of medicinal and nutritional importance. Ginseng has been used since ancient times for the treatment of numerous ailments as it has many therapeutic properties. Several phytoconstituents are present in <i>Panax ginseng</i> that possess a variety of beneficial pharmacological properties.</p><p><strong>Objective: </strong>To explore the potential of phytoconstituents of <i>Panax ginseng</i> in the treatment of depression, a molecular modeling technique was utilized targeting monoamine oxidase-A (MAO-A).</p><p><strong>Methods: </strong>A total of sixty-one phytoconstituents of ginseng were drawn with the help of ChemBioDraw Ultra 12.0 software and PDBs for MAO-A enzyme were retrieved from the RCSB PDB database. The prepared ligands were screened for MAO-A properties using the software Molegro Virtual Docker (MVD 2010.4.1.0). All the prepared ligands were evaluated for drug-likeliness properties using Swiss ADME.</p><p><strong>Results: </strong>Among the docking studies of 60 Ginseng phytochemicals including one standard, 15 phytoconstituents with the highest dock score and better binding interactions were selected further for absorption, distribution, metabolism and excretion (ADME) studies. Stachyose (-227.287, 17 interactions), Raffinose (-222.157, 14 interactions), and Ginsenoside Rg1 (-216.593, 10 interactions) were found to possess better interactions as compared to Clorgyline taken as a standard drug.</p><p><strong>Conclusion: </strong>Stachyose was found to be the most potent inhibitor of MAO-A enzyme under investigation and can be a potential lead molecule for the development of newer phytochemical-based treatment of depression.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"711-722"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Molecular Mechanism of Niuxi-Mugua Formula in Treating Coronavirus Disease 2019 <i>via</i> Network Pharmacology, Computational Biology, and Surface Plasmon Resonance Verification.","authors":"Wei Wang, Xu Cao, Yi-Nan Cao, Lian-Lian Liu, Shu-Ling Zhang, Wen-Ying Qi, Jia-Xin Zhang, Xian-Zhao Yang, Xiao-Ke Li, Xiao-Bin Zao, Yong-An Ye","doi":"10.2174/0115734099272592231004170422","DOIUrl":"10.2174/0115734099272592231004170422","url":null,"abstract":"<p><strong>Background: </strong>In China, Niuxi-Mugua formula (NMF) has been widely used to prevent and treat coronavirus disease 2019 (COVID-19). However, the mechanism of NMF for treating COVID-19 is not yet fully understood.</p><p><strong>Objective: </strong>This study aimed to explore the potential mechanism of NMF for treating COVID- 19 by network pharmacology, computational biology, and surface plasmon resonance (SPR) verification.</p><p><strong>Materials and methods: </strong>The NMF-compound-target network was constructed to screen the key compounds, and the Molecular Complex Detection (MCODE) tool was used to screen the preliminary key genes. The overlapped genes (OGEs) and the preliminary key genes were further analyzed by enrichment analysis. Then, the correlation analysis of immune signatures and the preliminary key genes was performed. Molecular docking and molecular dynamic (MD) simulation assays were applied to clarify the interactions between key compounds and key genes. Moreover, the SPR interaction experiment was used for further affinity kinetic verification.</p><p><strong>Results: </strong>Lipid and atherosclerosis, TNF, IL-17, and NF-kappa B signaling pathways were the main pathways of NMF in the treatment of COVID-19. There was a positive correlation between almost the majority of immune signatures and all preliminary key genes. The key compounds and the key genes were screened out, and they were involved in the main pathways of NMF for treating COVID-19. Moreover, the binding affinities of most key compounds binding to key genes were good, and IL1B-Quercetin had the best binding stability. SPR analysis further demonstrated that IL1B-Quercetin showed good binding affinity.</p><p><strong>Conclusion: </strong>Our findings provided theoretical grounds for NMF in the treatment of COVID-19.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"1113-1129"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}