In silico pharmacology最新文献_第8页

Molecular Docking and anti-MRSA effects of bioactive compounds from Cymbopogon. 锦葵生物活性化合物的分子对接及抗mrsa作用。

In silico pharmacology Pub Date : 2025-04-29 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00334-4

M Vinutha, A Manikandan, R N Lakshmikanth, S Shravani, B Divyashree, K Aishwarya, M M Nagaraj

{"title":"Molecular Docking and anti-MRSA effects of bioactive compounds from Cymbopogon.","authors":"M Vinutha, A Manikandan, R N Lakshmikanth, S Shravani, B Divyashree, K Aishwarya, M M Nagaraj","doi":"10.1007/s40203-025-00334-4","DOIUrl":"10.1007/s40203-025-00334-4","url":null,"abstract":"Molecular docking is an effective tool for screening bioactive compounds based on molecular mechanistic values. Efforts were taken to identify and screen plant secondary metabolites against Methicillin-Resistant Staphylococcus aureus (MRSA) using essential oil (EO) extracted from locally available species of Cymbopogon such as C. flexuosus, C. winterianus, and C. martinii. Hydro distillation of EO followed by GCMS characterization was accomplished. The library-generated compounds were docked against penicillin-binding protein 2a (PBP2a) (PDB ID: 3ZG5). We targeted PBP2a, a transpeptidase because it produces high-level resistance to MRSA against β-lactam antibiotics through its expression. Importantly, PBP2a catalyzes cell-wall cross-linking in the face of the defy by β-lactam antibiotics. A 100ns MD simulation was conducted to find the stability of the receptor-ligand complex. The anti-MRSA activity against different clinical isolates of MRSA was performed and the genetic similarity between the isolates of MRSA was analyzed through the RAPD technique which is a quick, cost-effective, and affordable technique.Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00334-4.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"73"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting immunogenic proteins of Zika virus for the prediction of immunoinformatics-driven circular mRNA vaccine model. 针对寨卡病毒免疫原性蛋白的免疫信息学驱动环状mRNA疫苗模型预测

In silico pharmacology Pub Date : 2025-04-25 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00362-0

Maryam Iftikhar, Ayesha Khattak, Nadeem Ahmad, Asifullah Khan, Zaheer Ul-Haq

{"title":"Targeting immunogenic proteins of Zika virus for the prediction of immunoinformatics-driven circular mRNA vaccine model.","authors":"Maryam Iftikhar, Ayesha Khattak, Nadeem Ahmad, Asifullah Khan, Zaheer Ul-Haq","doi":"10.1007/s40203-025-00362-0","DOIUrl":"10.1007/s40203-025-00362-0","url":null,"abstract":"Zika virus (ZIKV) is an arbovirus with single-stranded RNA that has become a major health concern worldwide, particularly in tropical and subtropical areas where it is transmitted by Aedes aegypti mosquitoes. Infection can leads to severe neurological complications, including microcephaly in infants and Guillain-Barré syndrome in adults. Due to the absence of a licensed vaccine, the current study was conceived to design a novel circular mRNA vaccine, capable of inducing an effective immune response by targeting the ZIKV proteins. Total 26 top-ranked epitopes (IC50 ≤ 100 nM) were prioritized from the conserved regions of ZIKV proteins. A multi-epitope construct was designed by incorporation of prioritized epitopes and β-defensin III adjuvant sequences to enhance immune activation. Molecular docking analysis revealed significant molecular interactions between the designed vaccine molecule and Toll-like receptors (TLRs), predicting an effective immune capability of the model vaccine. Molecular dynamics simulation validated the molecular and structural stability of the vaccine structure under physiological conditions. Immune simulations analysis predicted that the vaccine molecule could boost antibody production and is capable of achieving a global population coverage of 93.22%. Additionally, the circular mRNA vaccine design exhibited stability, with a minimum free energy (MFE) of - 1515.60 kcal/mol and a secondary centroid structure of - 1181.42 kcal/mol, speculating a resilient vaccine framework for potential ZIKV immunity.Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00362-0.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"72"},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In-silico screening, molecular dynamics simulation and ADME evaluation of Onosma bracteata Wall. for antiviral activity against Chandipura virus. 小苞草的硅晶筛选、分子动力学模拟及ADME评价。对钱迪普拉病毒的抗病毒活性

In silico pharmacology Pub Date : 2025-04-25 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00358-w

Bhavinkumar Gayakvad, Kshipra Chauhan, Vaibhav Bhatt, Devang J Pandya, Sanjay Chauhan, Dignesh Khunt, Udaykumar G Vegad

{"title":"In-silico screening, molecular dynamics simulation and ADME evaluation of Onosma bracteata Wall. for antiviral activity against Chandipura virus.","authors":"Bhavinkumar Gayakvad, Kshipra Chauhan, Vaibhav Bhatt, Devang J Pandya, Sanjay Chauhan, Dignesh Khunt, Udaykumar G Vegad","doi":"10.1007/s40203-025-00358-w","DOIUrl":"10.1007/s40203-025-00358-w","url":null,"abstract":"Chandipura Virus (CHPV) poses a significant public health challenge in India, specifically impacting children who are at a higher risk of developing Acute Encephalitis Syndrome (AES). There is a substantial lack of effective antiviral treatments for CHPV. This study delves into the potential antiviral properties of Onosma bracteata Wall., a traditional medicinal plant. Utilizing in-silico techniques, such as molecular docking with AutoDock Vina, and molecular dynamics simulations using GROMACS and SWISS-MODEL repository, we evaluated the interactions between the phytochemicals of O. bracteata and the N protein of CHPV. Our evaluation has uncovered several important compounds: Pulmonarioside C, Eritrichin, and P-Coumarinic Acid Ester of Trigonotin A. Phytochemicals including Pulmonarioside C, Eritrichin, and P-Coumarinic Acid Ester of Trigonotin A exhibited significant binding affinities of -8.7, -7.5, and -7.4 kcal/mol, respectively, with the N protein of CHPV. The binding energies exceed those of conventional antiviral medications, including Remdesivir (-7.4 kcal/mol) and Nevirapine (-6.0 kcal/mol). Nonetheless, the computational methods exhibit limitations, including insufficient accuracy in solvation effects and dependence on modeled proteins. Although the in-silico findings are encouraging, it is crucial to conduct experimental validation via in vitro and in vivo studies to verify their efficacy, as the experiments are conducted on a modelled protein. This study emphasizes the potential of integrating traditional medicine with computational tools to develop innovative antiviral therapies, despite existing limitations.Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00358-w.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"71"},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In silico analysis of Rutin and Morin against diabetes-associated molecular targets. 芦丁和桑辣素抗糖尿病相关分子靶点的计算机分析。

In silico pharmacology Pub Date : 2025-04-24 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00353-1

Rout George Kerry, Soumya Ranjan Mahapatra, Sanghamitra Nayak, Hemangini Naik, Kanika Kisku, Bijayananda Panigrahi, Namrata Misra, Sanatan Majhi

{"title":"In silico analysis of Rutin and Morin against diabetes-associated molecular targets.","authors":"Rout George Kerry, Soumya Ranjan Mahapatra, Sanghamitra Nayak, Hemangini Naik, Kanika Kisku, Bijayananda Panigrahi, Namrata Misra, Sanatan Majhi","doi":"10.1007/s40203-025-00353-1","DOIUrl":"10.1007/s40203-025-00353-1","url":null,"abstract":"Diabetes is one of the oldest diseases known to occur in humans and is regulated by a complex interplay of metabolic, genetic, and environmental factors. Several therapeutic options exist, including medications, exercise, improved health measures, psychological and mental well-being, and amelioration of disparity and depression. Current therapeutic options although are effective, they tends to display side effects that includes significant complications like gastrointestinal discomfort, decreased effectiveness and weight gain. Plant-derived bioactive substances with antidiabetic and/or hypoglycaemic properties have been found to be effective, however, the mechanism of action of the majority of herbs are still being characterized and standardized. However, in the present in-silico prediction for phytocompounds, Rutin (RU) and Morin (MO) revealed them to be more effective than or equal to conventional inhibitors in blocking the enzymes and receptors that contribute to diabetes development. Results of the in-silico investigations have clearly demonstrated the importance of RU and MO in binding diabetic-susceptible enzymes (alpha-amylase, DPP-4, and maltase-glucoamylase) and receptors (GLP-1R, SGLT1 and SGLT2). Additionally, in vitro antidiabetic enzymatic assays demonstrated the possible inhibitory activity of RU and MO against two diabetes-related molecular targets.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"68"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In silico drug repurposing of potential antiviral inhibitors targeting methyltransferase (2'-O-MTase) domain of Marburg virus. 针对马尔堡病毒甲基转移酶（2′-O-MTase）结构域的潜在抗病毒抑制剂的药物再利用。

In silico pharmacology Pub Date : 2025-04-24 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00355-z

Arkajit De, Swagath Subramanian, Prateek Nayak, Kuntal Pal

{"title":"In silico drug repurposing of potential antiviral inhibitors targeting methyltransferase (2'-O-MTase) domain of Marburg virus.","authors":"Arkajit De, Swagath Subramanian, Prateek Nayak, Kuntal Pal","doi":"10.1007/s40203-025-00355-z","DOIUrl":"10.1007/s40203-025-00355-z","url":null,"abstract":"Marburg Virus (MARV) presents a significant threat to human health, highlighting the urgent need for effective therapeutics. The MARV genome encodes a multifunctional 'large' L protein that plays a crucial role in polymerase, capping, and methyltransferase activities. Within this protein, the 2'-O-methyltransferase (2'-O-MTase) domain is essential for viral replication and immune evasion, making it a promising therapeutic target. However, the lack of structural data on this domain limits drug discovery efforts. To address this challenge, we utilized AlphaFold2 to predict a 3D structure of the MARV 2'-O-MTase domain. Molecular docking with its natural ligand, S-adenosyl methionine (SAM), allowed us to identify key active-site residues involved in ligand binding. We then screened 62 known inhibitors against this domain and identified four promising candidates: Lifirafenib (- 9.5 kcal/mol), Dolutegravir (- 8.5 kcal/mol), BRD3969 (- 8.3 kcal/mol), and JFD00244 (- 8.2 kcal/mol). Further, we assessed the pharmacokinetic and pharmacodynamic properties of these compounds to evaluate their drug-likeness. Molecular dynamics simulations, along with MM/GBSA free energy calculations, confirmed stable interactions between the selected inhibitors and the target domain. While these findings highlight promising candidates for MARV, experimental validation through in vitro and in vivo assays is essential to assess their safety and efficacy.Graphical abstract: Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00355-z.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"70"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combinational effect of metformin and mature coconut water on streptozotocin model of diabetes. 二甲双胍联合成熟椰子水对糖尿病链脲佐菌素模型的影响。

In silico pharmacology Pub Date : 2025-04-24 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00346-0

Oluwaseun Fapohunda, Ezekiel Olugbogi, Sunday O Usman, Iseoluwa J Apata

{"title":"Combinational effect of metformin and mature coconut water on streptozotocin model of diabetes.","authors":"Oluwaseun Fapohunda, Ezekiel Olugbogi, Sunday O Usman, Iseoluwa J Apata","doi":"10.1007/s40203-025-00346-0","DOIUrl":"10.1007/s40203-025-00346-0","url":null,"abstract":"Diabetes mellitus (DM) is a persistent metabolic disease typified by hyperglycemia, caused by insufficient or ineffective insulin. This study examined the therapeutic effects of metformin combined with coconut water. In this study, twenty male Wistar rats (150-220 g) were divided into four groups: normal control, diabetic control, diabetic treated with metformin, and diabetic treated with metformin plus coconut water. Diabetes was induced using nicotinamide and streptozotocin (STZ), followed by a 21-day oral treatment regimen. Body weight, fasting blood glucose levels, feed, and water intake were measured weekly. A molecular docking study was employed to assess the degree of affinity that compounds of coconut water have for important metabolic proteins. Combination therapies of metformin and coconut water significantly reduced the glucose levels in the blood when compared to the diabetic controls. Molecular docking revealed strong binding affinities between coconut water constituents, particularly chlorogenic acid, and key metabolic proteins, suggesting potential therapeutic effects. The study demonstrates that coconut water, in combination with metformin, effectively ameliorates hyperglycemia and enhances antioxidant enzyme activities in diabetic rats induced with STZ. These results imply that coconut water could serve as a beneficial adjunct treatment for managing DM.Graphical abstract: ","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"69"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Isoelectric point, net charge and amino acid analysis of experimentally validated therapeutic antibodies. 实验验证的治疗性抗体的等电点、净电荷和氨基酸分析。

In silico pharmacology Pub Date : 2025-04-17 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00356-y

Anil Kumar Nagraj, Riya Patel, Akshata Gavade, Roylan Pais, Pratibha Verma, Jaspal Patil

{"title":"Isoelectric point, net charge and amino acid analysis of experimentally validated therapeutic antibodies.","authors":"Anil Kumar Nagraj, Riya Patel, Akshata Gavade, Roylan Pais, Pratibha Verma, Jaspal Patil","doi":"10.1007/s40203-025-00356-y","DOIUrl":"10.1007/s40203-025-00356-y","url":null,"abstract":"The isoelectric point (pI) of an antibody is known to affect its non-specific interactions and repulsive self-interactions. However, analytical outcomes for the pI of a large number of therapeutic antibodies remain unexplored. In this study, we explored the pI and net charge of variable heavy (VH), variable light (VL), CDR (complementarity determining regions) and whole IgG on a large number of therapeutic antibodies, additionally amino acids distribution in the CDR regions were also analyzed. A total of 708 experimentally validated antibodies from the Thera-SAbDab database were analyzed in this study. Analysis of the antibody dataset showed that the pI of the whole IgG sequence is between 5 and 9, while the majority was in the intermediate range between 7 and 9 (86.7%). The charge had a wide range from - 10 to 12, with the majority falling between the charges 2-6 (53.4%). However, the combined pI score of the CDRs of light chains (60%) as well as for the heavy chains (67%) was observed in the range of 4-6. The amino acid composition analysis of CDR regions revealed that most of the amino acids in the light chain are uncharged-polar (46.3%) followed by hydrophobic-aliphatic (28.4%), while in the heavy chain; it is hydrophobic-aliphatic (35.2%) followed by uncharged-polar (24.6%). In conclusion, the pI and net charge analysis of therapeutic antibodies are crucial for understanding pharmacokinetic properties. Moreover, amino acid composition of the light and heavy chain CDR regions has a significant impact on the pI and charge of the entire IgG antibody.Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00356-y.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"66"},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational repurposing of polyphenols for anti-Mpoxviral activity. 多酚抗痘病毒活性的计算再利用。

In silico pharmacology Pub Date : 2025-04-17 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00345-1

Rishi Vachaspathy Astakala, Gagan Preet, Ahlam Haj Hasan, Ria Desai, Meshari Alfurayh, Rainer Ebel, Marcel Jaspars

{"title":"Computational repurposing of polyphenols for anti-Mpoxviral activity.","authors":"Rishi Vachaspathy Astakala, Gagan Preet, Ahlam Haj Hasan, Ria Desai, Meshari Alfurayh, Rainer Ebel, Marcel Jaspars","doi":"10.1007/s40203-025-00345-1","DOIUrl":"https://doi.org/10.1007/s40203-025-00345-1","url":null,"abstract":"Mpox is a globally prevalent disease that has triggered multiple epidemics over the past few decades, leading to moderate rates of hospitalisation and mortality. Recently, it has re-emerged in several countries, including the Democratic Republic of Congo, and appears to be spreading at an unprecedented pace. The disease is caused by zoonotic double-stranded DNA viruses. Due to its similarities with smallpox, distinguishing between the two can be challenging, though the smallpox vaccine typically provides immunity against Mpox. At the time of writing, no approved treatment for Mpox exists; however, several promising candidates have demonstrated the ability to inhibit viral replication, including resveratrol-a polyphenolic compound found in red wine. This study employs molecular docking and molecular dynamics simulations to assess the effectiveness and stability of nine resveratrol analogues. Additionally, 2D and 3D pharmacophore models were developed for the highest-ranked docked compounds, leading to a composite pharmacophore. A structure-activity relationship analysis was also conducted using these top-performing compounds. The findings suggest that two compounds- (9) [1,1'-biphenyl]-3,4',5-triol and (11) {3-hydroxy-5-[2-(4-hydroxyphenyl)ethenyl]phenyl}oxidanesulfonic acid-exhibit strong binding affinity, with compound 11 potentially forming a stable complex with the thymidylate kinase of the vaccinia virus.Graphical abstract: Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00345-1.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"65"},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drugs repurposed against morphine and heroin dependence: molecular docking, DFT, MM-GBSA-based MD simulation studies. 针对吗啡和海洛因依赖的药物：分子对接，DFT，基于mm - gbsa的MD模拟研究。

In silico pharmacology Pub Date : 2025-04-17 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00347-z

Jonaid Ahmad Malik, Mushtaq Ahmad Wani, Mohammad Ovais Dar, Prabha Garg, Javed N Agrewala

{"title":"Drugs repurposed against morphine and heroin dependence: molecular docking, DFT, MM-GBSA-based MD simulation studies.","authors":"Jonaid Ahmad Malik, Mushtaq Ahmad Wani, Mohammad Ovais Dar, Prabha Garg, Javed N Agrewala","doi":"10.1007/s40203-025-00347-z","DOIUrl":"10.1007/s40203-025-00347-z","url":null,"abstract":"Morphine and heroin dependence are growing concerns worldwide. Drug dependence is one of the greatest challenges, and developing alternative therapeutic strategies is essential. Due to few treatment options in pain management, morphine, a potent analgesic, is widely prescribed, but it carries a high risk of abuse. For the management of drug dependence, we have limited treatment options available, therefore, strategies should be developed to manage drug-seeking behaviors in clinical settings. We tried to find any FDA-approved drug targeting µ-opioid receptors through the in-silico approach. We screened around 186 FDA-approved drugs; we observed several drugs showing better docking scores with good affinity. We found vilazodone, indinavir, and lorazepam as potential drugs based on their affinity and mechanism of action. Later, these drugs were screened against human µ-opioid (PDB ID:8EF6) and other novel drug targets (5HT1 and TLR-4) that are associated with morphine dependence. Following docking, density functional theory (DFT), molecular dynamics (MD), molecular mechanics, and general born surface area (MM-GBSA) were performed to calculate the stability and ligand-protein binding free energies. Vilazodone, indinavir and lorazepam showed promising docking, MD, the energy gap between the HOMO and LUMO chemical reactivity, and MM-GBSA results compared to morphine and naloxone. We propose that these three drugs have huge potential to reverse the morphine and heroin dependence in diseased subjects near future.Graphical abstract: Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00347-z.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"67"},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In silico analysis of zosurabalpin-LptB2FG binding in Acinetobacter spp., Klebsiella pneumoniae, and Shigella flexneri: mechanisms underlying its differential efficacy. zosurabalpin-LptB2FG在不动杆菌、肺炎克雷伯菌和福氏志贺氏菌中的结合：其不同疗效的机制。

In silico pharmacology Pub Date : 2025-04-16 eCollection Date: 2025-01-01 DOI: 10.1007/s40203-025-00343-3

Meryam Magri, Rachid Eljaoudi, Lahcen Belyamani, Azeddine Ibrahimi, El Mehdi Bouricha

{"title":"In silico analysis of zosurabalpin-LptB2FG binding in Acinetobacter spp., Klebsiella pneumoniae, and Shigella flexneri: mechanisms underlying its differential efficacy.","authors":"Meryam Magri, Rachid Eljaoudi, Lahcen Belyamani, Azeddine Ibrahimi, El Mehdi Bouricha","doi":"10.1007/s40203-025-00343-3","DOIUrl":"10.1007/s40203-025-00343-3","url":null,"abstract":"Zosurabalpin, a novel tethered macrocyclic peptide antibiotic, exhibits potent activity against Acinetobacter spp., particularly carbapenem-resistant Acinetobacter baumannii (CRAB). Zosurabalpin inhibits lipopolysaccharide (LPS) transport by targeting the LptB2FG protein complex, resulting in toxic LPS accumulation and bacterialdeath. This study investigates zosurabalpin's molecular specificity against Acinetobacter spp., its ineffectiveness against Klebsiella pneumoniae, and its potential efficacy against Shigella flexneri. Comparative analysis of LptB2FG sequences and structures, revealed significant differences in LptB2FG protein conformations, pocket geometry and electrostatic surface surrounding the binding pocket among the three species, which may influence zosurabalpin binding. Docking results for zosurabalpin showed lower binding affinities for K. pneumoniae and S. flexneri compared to Acinetobacter baylyi. Additionally, other zosurabalpin derivatives were tested showing improved binding affinities for K. pneumoniae but not for S. flexneri. These findings underscore the need for tailored zosurabalpin derivatives to enhance efficacy against a broader spectrum of Gram-negative bacteria.Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00343-3.","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"62"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0