Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Chemical exploration of different extracts from <i>Phytolacca americana</i> leaves and their potential utilization for global health problems: <i>in silico</i> and network pharmacology validation.","authors":"Nouran M Fahmy, Shaimaa Fayez, Gokhan Zengin, Selami Selvi, Abdullahi Ibrahim Uba, Adriano Mollica, Abdelhakim Bouyahya, Sathish Kumar M Ponniya, Nilofar, Sabrina Lekmine, Claudio Ferrante, Omayma A Eldahshan","doi":"10.1080/07391102.2024.2308770","DOIUrl":"10.1080/07391102.2024.2308770","url":null,"abstract":"<p><p><i>Phytolacca americana</i> L. is of great interest as a traditional additive in various folk remedies in several countries, including Turkey. We aimed to determine the chemical profile (assisted by high-Performance liquid chromatography-electrospray ionization-tandem mass apectrometry (HPLC-ESI-MS/MS) experiments of three extracts obtained by different polarity solvents viz. ethyl acetate (to extract semipolar compounds), methanol and water (to extract highly polar metabolites) from <i>P. americana</i> leaves. Their anti-diabetic effects were investigated <i>in vitro</i> by assessing their inhibition toα-amylase and α-glucosidase. Assessment of the neuroprotective potential of the three extracts was carried out against acetyl-(AChE) and butyryl-(BChE) cholinesterase enzymes. HPLC-ESI-MS/MS experiments showed a total of 17 chromatographic peaks primarily classified to six flavonoids, two saponins, and six fatty acids. Antioxidant assays revealed remarkable activity for the ethyl acetate and methanol extracts. The BChE inhibition was considerably more significant (4.08 mg galantamine equivalent (GALAE)/g) for the ethyl acetate extract, whereas the methanol extract had good inhibitory efficacy for AChE (2.05 mg GALAE/g). Through network pharmacology, the compounds' mechanism of action of targeted key gene in their associated diseases were identified. The hubb gene signal transducer and activator of transcription 3 (STAT3) and tumour necrosis factor (TNFα) where the <i>P. americana compound's</i> site of action in inflammation bowel disease. The results offer possibilities for the prospective application of <i>P. americana</i> in metabolic regulation, blood glucose control, and as a source of bioactive compounds with cholinesterase enzyme inhibitory characteristics which could be of relevance in the cosmetic or pharmaceutical industry for combating melanogenesis.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5178-5198"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In-vitro</i> and <i>in-silico</i> exploration of glycogen phosphorylase inhibition by <i>Aloe sinkatana</i> anthraquinones.","authors":"Mohnad Abdalla, Gihan Elhassan, Asaad Khalid, Muhammad Shafiq, Syeda Sumayya Tariq, Meshari A Alsuwat, Fatima Elfatih, Sakina Yagi, Hassan H Abdallah, Mohamad Fawzi Mahomoodally, Zaheer Ul-Haq","doi":"10.1080/07391102.2025.2524404","DOIUrl":"https://doi.org/10.1080/07391102.2025.2524404","url":null,"abstract":"<p><p>Glycogen phosphorylase (GP), a glycosyltransferase protein, was the initial allosteric enzyme identified and has since undergone thorough characterization. GP regulates the intracellular metabolization of glycogen thereby regulating blood glucose levels. Any dysfunction in this process results in altered blood glucose levels, such as Diabetes Mellitus (DM). Anthraquinones isolated from <i>Aloe sinkatana</i> have been found to possess several medicinal benefits. In this study, in-vitro techniques and computational tools were utilized to study in-depth the potential of inhibiting effects of <i>A. sinkatana</i> anthraquinones on GP. Two anthraquinones were isolated for this purpose. Their structures were elucidated and the possible effect on phosphorylase activity was assessed via an enzyme inhibition assay, where both the compounds showed substantial inhibitory activity against GP. The minimal difference between HOMO and LUMO energy levels further supported their potential binding, in line with DFT results. The binding modes and interactions were further explored in detail using in-silico studies via molecular docking and MD simulation. Results revealed strong protein-ligand interactions with Asn284 and Glu382, indicating stability. The deviations (RMSD) and fluctuations (RMSF) remained consistent, with RMSD averaging 2.2Å and RMSF around 1.5 Å. Compounds A and B are effectively bound to the receptor's active site, with -58.63 and -59.65 kcal/mol binding free energies recorded, suggesting potent GP inhibition potential. QSAR analysis revealed positive Log P values, indicating their lipophilic nature, and adhered to Lipinski's rule of 5. In conclusion these anthraquinones showed strong potential in controlling chronically elevated blood sugar levels which could help in the management of DM.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology and molecular dynamic simulation integrated strategy for the screening of active components and mechanisms of phytochemicals from <i>Datura innoxia</i> on Alzheimer and cognitive decline.","authors":"Mubarak A Alamri, Muhammad Tahir Ul Qamar","doi":"10.1080/07391102.2024.2308756","DOIUrl":"10.1080/07391102.2024.2308756","url":null,"abstract":"<p><p>Alzheimer's disease (AD) ranks as the most prevalent neurodegenerative disorder with dementia and it accounts for more than 70% of all cases. Despite extensive reporting on the experimental investigation of <i>Datura innoxia</i> (DI) and its phytochemical components in the treatment of AD, the urgent need for elucidation of the principle of multi-mechanism and multi-level treatment of AD remains. In this research, molecular docking and network pharmacology were used to evaluate active compounds and molecular targets of DI for the treatment of AD. The phytochemical compounds of DI were obtained from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) as well as the Traditional Chinese Medicine System Pharmacology (TCMSP) databases. The screening includes the 28 most abundant components of DI and the Swiss Target Prediction database was used to predict targets of these compounds. The GeneCards database was used to collect AD-related genes. Both DI and AD targets were imported into a Venn diagram, and the 28 overlapped genes were identified as potential DI anti-AD targets. The results showed that Dinoxin B, Meteloidine, Scopoline, and Tropic acid had no effect on AD-related genes. Furthermore, the GO enrichment analysis indicates that DI influences molecular functions and biological processes such as learning or memory and modulation of chemical synaptic transmission as well as the membrane raft and membrane microdomain. The KEGG pathway analysis revealed that the key pathways implicated in DI's anti-AD actions include serotonergic synapse, IL-17 signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Based on the STRING and Cytoscape network-analysis platforms, the top ten anti-AD core targets include APP, CASP3, IL6, BACE1, IL1B, ACE, PSEN1, GAPDH, GSK3B and ACHE. The molecular docking and molecular dynamic simulation of the top two molecules against the top three target proteins confirmed the strong binding affinity and stability at the docked site. Overall, our findings pave the path for further research into the development and optimization of potential anti-AD agents from DI.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5296-5312"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An ensemble docking-based virtual screening and molecular dynamics simulation of phytochemical compounds from Malaysian Kelulut Honey (KH) against SARS-CoV-2 target enzyme, human angiotensin-converting enzyme 2 (ACE-2).","authors":"Che Muhammad Khairul Hisyam Ismail, Azzmer Azzar Abdul Hamid, Nur Nadiah Abdul Rashid, Widya Lestari, Khairani Idah Mokhtar, Basma Ezzat Mustafa Alahmad, Mohd Ridzuan Mohd Abd Razak, Azlini Ismail","doi":"10.1080/07391102.2024.2308762","DOIUrl":"10.1080/07391102.2024.2308762","url":null,"abstract":"<p><p>The human angiotensin-converting enzyme 2 (ACE-2) receptor is a metalloenzyme that plays an important role in regulating blood pressure by modulating angiotensin II. This receptor facilitates SARS-CoV-2 entry into human cells <i>via</i> receptor-mediated endocytosis, causing the global COVID-19 pandemic and a major health crisis. Kelulut honey (KH), one of Malaysian honey recently gained attention for its distinct flavour and taste while having many nutritional and medicinal properties. Recent study demonstrates the antiviral potential of KH against SARS-CoV-2 by inhibiting ACE-2 <i>in vitro</i>, but the bioactive compound pertaining to the ACE-2 inhibition is yet unknown. An ensemble docking-based virtual screening was employed to screen the phytochemical compounds from KH with high binding affinity against the 10 best representative structures of ACE-2 that mostly formed from MD simulation. From 110 phytochemicals previously identified in KH, 27 compounds passed the ADMET analysis and proceeded to docking. Among the docked compound, SDC and FMN consistently exhibited strong binding to ACE-2's active site (-9.719 and -9.473 kcal/mol) and allosteric site (-7.305 and -7.464 kcal/mol) as compared to potent ACE-2 inhibitor, MLN 4760. Detailed trajectory analysis of MD simulation showed stable binding interaction towards active and allosteric sites of ACE-2. KH's compounds show promise in inhibiting SARS-CoV-2 binding to ACE-2 receptors, indicating potential for preventive use or as a supplement to other COVID-19 treatments. Additional research is needed to confirm KH's antiviral effects and its role in SARS-CoV-2 therapy, including prophylaxis and adjuvant treatment with vaccination.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5393-5422"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of 1H-pyrazolo[3,4-<i>b</i>]pyrazine derivatives as selective allosteric inhibitor of protein tyrosine phosphatase SHP2 for the treatment of KRAS^G12C-mutant non-small cell lung cancer.","authors":"Wen-Qiang Xu, Shi-Zhou Qi, Ji-Feng Zhao, Li-Peng Li, Chuan-Hua Ding, Wen-Shan Liu","doi":"10.1080/07391102.2024.2308771","DOIUrl":"10.1080/07391102.2024.2308771","url":null,"abstract":"<p><p>The high expression or mutation of SHP2 can induce cancer, so targeting SHP2 has become a new strategy for cancer treatment. In this study, we used the previously reported SHP2 allosteric inhibitor IACS-13909 as a lead drug for structural derivation and modification, and synthesized three SHP2 inhibitors. Among them, 1<i>H</i>-pyrazolo[3,4-<i>b</i>]pyrazine derivative 4b was a highly selective SHP2 allosteric inhibitor, with an IC₅₀ value of 3.2 nM, and its inhibitory activity was 17.75 times than that of the positive control IACS-13909. The cell proliferation experiment detected that compound 4b would markedly inhibit the proliferation of various cancer cells. Interestingly, compound 4b was highly sensitive to KRAS^G12C-mutant non-small cell lung cancer NCI-H358 cells, with an IC₅₀ value of 0.58 μM and its antiproliferative activity was 4.79 times than that of IACS-13909. Furthermore, the combination therapy of compound 4b and KRAS^G12C inhibitor sotorasib would play a strong synergistic effect against NCI-H358 cells. The western blot experiment detected that compound 4b markedly downregulated the phosphorylation levels of ERK and AKT in NCI-H358 cells. Molecular docking study predicted that compound 4b bound to the allosteric site of SHP2 and formed H-bond interactions with key residues Thr108, Glu110, Arg111, and Phe113. In summary, this study aims to provide new ideas for the development of SHP2 allosteric inhibitors for the treatment of KRAS^G12C mutant non-small cell lung cancer.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5465-5473"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of novel isoxazole derivatives as tubulin inhibitors using computer-aided techniques: QSAR modeling, <i>in silico</i> ADMETox, molecular docking, molecular dynamics, biological efficacy, and retrosynthesis.","authors":"Youness Moukhliss, Yassine Koubi, Imran Zafar, Marwa Alaqarbeh, Hamid Maghat, Abdelouahid Sbai, Tahar Lakhlifi, Mohammed Bouachrine","doi":"10.1080/07391102.2024.2306493","DOIUrl":"10.1080/07391102.2024.2306493","url":null,"abstract":"<p><p>In the current work, computational methods were used to investigate new isoxazole derivatives that could be used as tubulin inhibitors. The study aims to develop a reliable quantitative structure-activity relationship (QSAR) model, following the criteria set by Golbraikh, Tropsha, and Roy. As a result, seven candidate compounds were developed, all having higher activity than the well-established anticancer agent Cisplatin (Cisp). According to the ADMETox <i>in silico</i> test, the candidates <b>Pr4</b>, <b>Pr5</b>, and <b>P6</b> can be toxic. As a result, we have chosen to focus our study on compounds <b>Pr1</b>, <b>Pr2</b>, and <b>Pr3</b>. Molecular docking analysis revealed that drug candidate <b>Pr2</b> exhibits the highest stability within the oxidized quinone reductase 2 (PDB ID: 4zvm), target receptor (ΔG(<b>Pr2</b>) = ΔG(Pr3) = -10.4 < ΔG(<b>Pr1</b>) = -10.0 < ΔG(Cisp) = -7.3 kcal/mol). This finding aligns with the activity predictions made by the QSAR model. Furthermore, molecular dynamics simulations of the Pr2-4zvm complex over 100 ns confirm the ligand's robust stability within the receptor's active site, supporting the results obtained from molecular docking and the QSAR model predictions. The CaverDock software was utilized to identify the tunnels likely to be followed by ligands moving from the active site to the receptor surface. This analysis also helped in determining the biological efficacy of the target compounds. The results indicated that the <b>Pr2</b> compound is more effective than the others. Finally, the computer-assisted retrosynthesis process of two high confidence sequences was used to synthesize drug candidates.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4997-5008"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational analysis of consanguineous families and their targeted therapy against dwarfism.","authors":"Feroz Khan, Sarmir Khan, Nehal Rana, Tariq Rahim, Abida Arshad, Imtiaz Khan, Hanan A Ogaly, Dalia Abd El Moneim Ahmed, Ayed A Dera, Sumera Zaib","doi":"10.1080/07391102.2024.2307446","DOIUrl":"10.1080/07391102.2024.2307446","url":null,"abstract":"<p><p>Dwarfism is a medical term used to describe individuals with a height-vertex measurement that falls below two standard deviations (-2SD) or the third percentile for their gender and age. Normal development of growth is a complicated dynamic procedure that depends upon the coordination of different aspects involving diet, genetics, and biological aspects like hormones in equilibrium. Any severe or acute pathologic procedure may disturb the individual's normal rate of growth. In this research, we examined four (A-D) Pakistani consanguineous families that exhibited syndromic dwarfism, which was inherited in an autosomal recessive pattern. The genomic DNA of each family member was extracted by using phenol-chloroform and Kit methods. Whole Exome Sequencing (WES) of affected family members (IV-11, III-5, IV-4 and III-13) from each group was performed at the Department of Medical Genetics, University of Antwerp, Belgium. After filtering the exome data, the mutations in <i>PPM1F, FGFR3, ERCC2,</i> and <i>PCNT</i> genes were determined by Sanger sequencing of each gene by using specific primers. Afterward, <i>FGFR3</i> was found to be a suitable drug target among all the mutations to treat achondroplasia also known as disproportionate dwarfism. BioSolveIT softwares were used to discover the lead active inhibitory molecule against <i>FGFR3</i>. This research will not only provide short knowledge to the concerned pediatricians, researchers, and family physicians for the preliminary assessment and management of the disorder but also provide a lead inhibitor for the treatment of disproportionate dwarfism.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4910-4927"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated computational and experimental evaluation of phenolic constituents of <i>Apricot fruit</i> L. for antiqourum sensing, antibiofilm, antioxidant, and 15-lox inhibitory properties.","authors":"Hafiz Abdul Rafey, Mohamed El-Shazly, Tooba Khalid, Tanveer Alam, Shah Iram Niaz, Omer Farooq","doi":"10.1080/07391102.2024.2309334","DOIUrl":"10.1080/07391102.2024.2309334","url":null,"abstract":"<p><p>The present study investigated the antioxidant profile together with the antibacterial potential of Apricot L. with the aim to find a functional food based anti-infective lead. Additionally the study evaluated the biofilm and QS inhibitory potential of the plant using <i>Pseudomonas aeruginosa</i> (ATCC 15442) and <i>Chromo bacterium Violaceum</i> (DSM 30191) respectively. Several fractions of the peel of <i>Apricot</i> were subjected to initial antimicrobial and antibiofilm screening. Among all the fractions, methanol and ethyl acetate fractions displayed significant antimicrobial activity against the strains selected with MIC values 1.25 mg/dL and 1.68 mg/dL respectively. Similarly, while evaluating antiqourum-sensing potential, methanol extract showed remarkable zone of inhibition (14mm) with Violaceum inhibition (58%) while aqueous part presented moderately good inhibition (32%) with zone of inhibition of (4mm). N-hexane fraction was least active in this regard. In case of free radicals scavenging aptitudes, Ethanolic fraction displayed the highest free radicals scavenging potential (IC50μg/mL 13.76 ± 23.61) while Aqueous and ethyl acetate part exhibited moderate to good antioxidant behaviors with IC50μg/mL of 26.74 ± 22.00 and 19.49 ± 2.91 respectively. Then the selected compounds were screened for putative binding sites and molecular docking studies followed by enzyme inhibition assays. The negative binding energies and close proximity to residues in the binding pocket of selected targets including human α- soybean lox (PDB ID 1IK3), quorum sensing regulators LasR (2UV0) were observed which indicated high affinity and tight binding capacity of compounds <b>1</b> and <b>5</b> towards the active sites of LasR 2UV0 and 15-lipoxygenase. The physicochemical characteristics and toxicity expectation were computationally accomplished. Bioactivity prediction study revealed that all of the selected Phytoconstituents displayed incredible Bioactivity score. None of the selected chemical compound was found to be toxic as discovered by toxicity studies. Compound <b>4</b> exhibited the highest inhibition of 15-lipoxygenase <i>in vitro</i> (69%, at 0.037 mM final concentration) and that is accompanied by compound <b>5</b> (60%) whereas in the biofilm inhibition assay, compound <b>1</b> was most active (IC50 0.05 mM), followed by compound <b>3</b> (IC50 0.07 mM). It was therefore determined that compounds <b>1</b> and <b>3</b> had the highest biofilm inhibitory activity, whereas compounds <b>4</b> and <b>5</b> were potent 15-lipoxygenase inhibitors with potentially anti-inflammatory properties. Future investigations are suggested for the characterization and formulation development.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5124-5132"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-driven covalent drug design strategies targeting main protease (m^pro) against SARS-CoV-2: structural insights and molecular mechanisms.","authors":"Mohammad Hossein Haghir Ebrahim Abadi, Abdulrahman Ghasemlou, Fatemeh Bayani, Yahya Sefidbakht, Massoud Vosough, Sina Mozaffari-Jovin, Vladimir N Uversky","doi":"10.1080/07391102.2024.2308769","DOIUrl":"10.1080/07391102.2024.2308769","url":null,"abstract":"<p><p>The emergence of new SARS-CoV-2 variants has raised concerns about the effectiveness of COVID-19 vaccines. To address this challenge, small-molecule antivirals have been proposed as a crucial therapeutic option. Among potential targets for anti-COVID-19 therapy, the main protease (M^pro) of SARS-CoV-2 is important due to its essential role in the virus's life cycle and high conservation. The substrate-binding region of the core proteases of various coronaviruses, including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), could be used for the generation of new protease inhibitors. Various drug discovery methods have employed a diverse range of strategies, targeting both monomeric and dimeric forms, including drug repurposing, integrating virtual screening with high-throughput screening (HTS), and structure-based drug design, each demonstrating varying levels of efficiency. Covalent inhibitors, such as Nirmatrelvir and MG-101, showcase robust and high-affinity binding to Mpro, exhibiting stable interactions confirmed by molecular docking studies. Development of effective antiviral drugs is imperative to address potential pandemic situations. This review explores recent advances in the search for M^pro inhibitors and the application of artificial intelligence (AI) in drug design. AI leverages vast datasets and advanced algorithms to streamline the design and identification of promising M^pro inhibitors. AI-driven drug discovery methods, including molecular docking, predictive modeling, and structure-based drug repurposing, are at the forefront of identifying potential candidates for effective antiviral therapy. In a time when COVID-19 potentially threat global health, the quest for potent antiviral solutions targeting M^pro could be critical for inhibiting the virus.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5436-5464"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient microwave synthesis of flurbiprofen derivatives and their enhancement of efficacy in chronic inflammatory pain models and gastro-protective potential in post-operative model.","authors":"Nisar Zamin Shah, Ajmal Khan, Sobia Ahsan Halim, Satya Kumar Avula, Nazar Ul Islam, Imran Khan, Nasiara Karim, Muhammad Kifayatullah, Asaad Khalid, Hassan A Alhazmi, Ashraf N Abdalla, Hamdy Kashtoh, Ahmed Al-Harrasi","doi":"10.1080/07391102.2024.2309645","DOIUrl":"10.1080/07391102.2024.2309645","url":null,"abstract":"<p><p>Present research was designed to synthesize and characterize the flurbiprofen derivatives and to evaluate their analgesic, anti-inflammatory and gastro-protective activities in post-operative and chronic inflammatory pain models. Flurbiprofen derivatives were produced by using three-step processes involving esterification, hydrazide production, and schiff base, each of which modified a different carboxyl group. All the newly synthesized flurbiprofen derivatives (<b>NS5-NS8</b>) were characterized by ¹H NMR,¹³C NMR,¹⁹F NMR and HR-ESI-MS, and the post-operative, inflammatory pain and ulcerogenic activities were determined in well-established <i>in-vivo</i> animal models. To evaluate post-operative and inflammatory pain, various doses of compounds [1, 3, 10, and 30 mg/kg (bwt)] were used, while their ulcerogenic potential was assessed at doses of 100 and 150 mg/kg (bwt). The incisional damage linked pain was significantly (<i>p</i> < 0.001) reduced by derivatives at different doses in both the acute and repeated tests with decreased response of phologistic agent-induced inflammation. The stomach histology and biochemical features demonstrate that the synthesized derivatives have no potential to cause ulcerogenicity as compared to aspirin and flurbiprofen. Furthermore, docking shows that the hydrazide moiety of these compounds is crucial in interacting within COX-2 binding site. Therefore, the synthesized compounds exhibit strong analgesic and anti-inflammatory effects and a low risk of causing ulcers. These attributes render them potentially valuable therapeutic agents for the treatment of pathological disorders associated with inflammation and pain.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5536-5551"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}