In silico pharmacology最新文献

{"title":"Repurposing doxycycline for the inhibition of monkeypox virus DNA polymerase: a comprehensive computational study.","authors":"Muhammad Abrar Yousaf, Maurice Michel, Abeedha Tu-Allah Khan, Misbah Noreen, Saddia Bano","doi":"10.1007/s40203-025-00307-7","DOIUrl":"10.1007/s40203-025-00307-7","url":null,"abstract":"<p><p>The global spread of monkeypox, caused by the double-stranded DNA monkeypox virus (MPXV), has underscored the urgent need for effective antiviral treatments. In this study, we aim to identify a potent inhibitor for MPXV DNA polymerase (DNAP), a critical enzyme in the virus replication process. Using a computational drug repurposing approach, we performed a virtual screening of 1615 FDA-approved drugs based on drug-likeness and molecular docking against DNAP. Among these, 1430 compounds met Lipinski's rule of five for drug-likeness, with Doxycycline emerging as the most promising competitive inhibitor, binding strongly to the DNAP active site with a binding affinity of - 9.3 kcal/mol. This interaction involved significant hydrogen bonds, electrostatic interactions, and hydrophobic contacts, with Doxycycline demonstrating a stronger affinity than established antivirals for smallpox, including Cidofovir, Brincidofovir, and Tecovirimat. Stability and flexibility analyses through a 200 ns molecular dynamics simulation and normal mode analysis confirmed the robustness of Doxycycline binding to DNAP. Overall, our results suggest Doxycycline as a promising candidate for monkeypox treatment, though additional experimental and clinical studies are needed to confirm its therapeutic potential and clinical utility.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00307-7.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"27"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434027","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}

{"title":"<i>Tinospora cordifolia</i> bioactive compounds as a novel sterol 14a-demethylase (CYP51) inhibitor: an in silico study.","authors":"Kolawole T Mesileya, Precious C Onyeka, Iyidola M Adaramola, Quareebat O Igbalaye, Damilola S Bodun, Wisdom K Alao, Salim Y Jibril, Mustapha S Mohammed, Adedayo S Bowaje, Adebisi M Adeleye, Olaposi I Omotuyi","doi":"10.1007/s40203-025-00312-w","DOIUrl":"10.1007/s40203-025-00312-w","url":null,"abstract":"<p><p><i>Trypanosoma cruzi</i>, the causative agent of Chagas disease, poses a life-threatening risk in both endemic and non-endemic regions. The parasite's survival depends on the production of sterols via the 14-α-demethylase (CYP51) metabolic pathway. Current treatments for Chagas disease are often associated with undesirable side effects and drug resistance. This study aimed to identify potential inhibitors of CYP51 using bioactive compounds derived from <i>Tinospora cordifolia</i>. A library of 122 compounds from <i>T. cordifolia</i> was screened against CYP51 using the Glide docking model in the Maestro-Schrodinger suite (2022). The top four leads were evaluated through e-pharmacophore modeling, pharmacokinetics (ADMET) analysis and molecular mechanics generalized Born surface area (MM-GBSA) calculations. The top four compounds exhibited superior binding affinity to CYP51 compared to the standard drug, benznidazole, with docking scores ranging from - 11.397 kcal/mol to - 9.539 kcal/mol. ADMET predictions suggested low cytotoxicity for these compounds. Among the leads, epicatechin and n-trans-caffeoyl tyramine showed the greatest stability, reduced flexibility, and compact conformations, making them promising candidates for further investigation. This study identifies potential inhibitors from <i>T. cordifolia</i> with high binding affinity and structural compatibility with CYP51. While these results are encouraging, further in vivo and in vitro studies are necessary to validate their efficacy as anti-Chagas agents.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00312-w.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"28"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434814","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}

{"title":"In-silico evaluation of diffractaic acid as novel anti-diabetic inhibitor against dipeptidyl peptidase IV enzyme.","authors":"Miah Roney, Abdul Rashid Issahaku, Amit Dubey, Aisha Tufail, S M Istiaque Hamim, Anke Wilhelm, Mohd Fadhlizil Fasihi Mohd Aluwi","doi":"10.1007/s40203-025-00321-9","DOIUrl":"10.1007/s40203-025-00321-9","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is one of the most common long-term metabolic illnesses with detrimental implications on health and 90-95% of DM cases worldwide are caused by type 2 diabetes (T2DM). The side effects of the existing medicines include vomiting, diarrhea, and serious damage to the kidneys, blood vessels, and nerves. Therefore, finding anti-diabetic medications without side effects is crucial. The main goal of this work is to find anti-diabetic inhibitors using in-silico evaluation techniques such as molecular docking, molecular dynamic simulation, principal component analysis, and drug probability analysis. The DPP-IV is one of numerous molecular targets implicated in the pathogenesis of DM and Diffractaic acid (DF) was docked into the active site of this enzyme to assess the inhibitory effect of DF. In addition, MD simulation and PCA were used to assess the stability of docked complex. Furthermore, the DF was then subjected to drug probability investigations. The binding affinity of the DF was - 40.2476 kcal/mol, which was comparable to the reference compound (- 43.0908 kcal/mol). Furthermore, the compound was in a stable structure, as demonstrated by MD simulation and PCA analysis. Based on drug probability tests, DF also demonstrated druggable qualities. The results of this investigation suggest that DF may function as a possible inhibitor against DM; nevertheless, more in vitro and in vivo investigations are required to validate the activity and other properties.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00321-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412119","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}

{"title":"Molecular detection of <i>mecA</i> gene from methicillin-resistant <i>Staphylococcus aureus</i> isolated from clinical and environmental samples and its potential inhibition by phytochemicals using in vitro and in silico approach.","authors":"Mohammed M Mohammed, Mustafa Alhaji Isa, Mustapha B Abubakar, Abubakar Sadiq Baba Dikwa, Abidemi Paul Kappo","doi":"10.1007/s40203-024-00297-y","DOIUrl":"10.1007/s40203-024-00297-y","url":null,"abstract":"<p><p>The increasing prevalence of Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) has posed significant challenges in clinical and environmental settings. MRSA's resistance is attributed to the <i>mecA</i> gene, which encodes the penicillin-binding protein 2a (PBP2a), conferring resistance to β-lactam antibiotics. This study aimed to molecularly detect the <i>mecA</i> gene in MRSA isolates from clinical and environmental samples and identify potential inhibitors of PBP2a using in vitro and in silico approaches. A total of 180 samples were collected, isolating 64 <i>Staphylococcus aureus</i> strains, of which 10 (37%) were confirmed as MRSA. Molecular detection confirmed the presence of the <i>mecA</i> gene in these isolates. Phytochemical analysis of <i>Acacia nilotica</i> and <i>Mangifera indica</i> extracts revealed bioactive compounds with antimicrobial properties. In vitro antimicrobial testing showed the plant extracts demonstrated significant inhibitory effects against MRSA, with minimum inhibitory concentrations (MIC) ranging from 0 to 6.20 mg/mL. Molecular docking and molecular dynamics simulation analyses identified three compounds (CID_628694, CID_546930, and CID_620007) with strong binding affinities and stable interactions with PBP2a, suggesting their potential as novel inhibitors. These findings highlight the therapeutic potential of phytochemicals in combating MRSA and provide a basis for future experimental validations.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"26"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401042","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}

{"title":"Prediction of SafD adhesin strong binding peptides for pilus proteins assembly suppression in the prevention of <i>Salmonella</i>-induced biofilm formation using virtual mutagenesis studies.","authors":"Priyanka Samanta, Sourav Ghorai","doi":"10.1007/s40203-025-00313-9","DOIUrl":"10.1007/s40203-025-00313-9","url":null,"abstract":"<p><p>Clinical isolates of <i>Salmonella enterica</i> contain Saf pili that establish initial bacterial attachment with the human epithelium to form biofilms which are a common cause of several abdominal complications. Due to the rise in antibiotic-resistant strains of bacteria, an alternate strategy of inhibiting the initial bacterial contact with the epithelial layers is well-studied. Saf pili undergo a chaperone-usher pathway assembly mechanism to generate its host-recognizing functional form, SafDAA. Preventing the biogenesis of the pili by targeting the SafD and SafA proteins polymerization will prevent host recognition. In this study, virtual mutagenesis studies using the recently reported X-ray crystal structure of an N-terminal peptide co-crystallized with SafD led to the design of peptides that exhibit enhanced binding with SafD compared to its native peptide. Virtual alanine mutagenesis and protein-peptide interaction studies identified several hotspot residues. Molecular dynamics simulations and binding free energy calculations identified key pairwise interactions between the designed peptides and SafD. In addition, a library of 110 peptides that are predicted to bind strongly with SafD is prepared which can serve as an excellent resource for the discovery of novel SafD-binding peptides. This work provided new insights into the design of novel anti-virulence therapies targeting <i>Salmonella enterica</i>.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00313-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"25"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412120","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}

{"title":"Computer aided design of inhibitor molecules against Vpr protein from different HIV-1 subtypes.","authors":"Joyeeta Datta, Satyabrata Majumder, Kalyan Giri","doi":"10.1007/s40203-025-00318-4","DOIUrl":"10.1007/s40203-025-00318-4","url":null,"abstract":"<p><p>HIV-1 is a retrovirus that affects the human immune system and consequently leads to the development of AIDS. The high mutation rate in HIV-1 produces different subtypes which underscores the development of new therapeutics against it. This study aims to develop a novel small molecule that can be used as a potential inhibitor against the Vpr protein of all the subtypes of HIV-1. The druggable pockets of the Vpr protein of each subtype were identified and the conformational stability of these pockets was studied. The structure-based Drug Design method was used to design small molecules against the high-scoring pocket from each subtype individually using AutoGrow4 software. Molecules with strong binding affinity were selected from each subtype individually and binding affinity was checked for all the subtypes. Considering druggability and ADMET properties, we have identified two novel molecules that act as potential Vpr protein inhibitors. Both the molecules were shown to form stable complexes with the Vpr proteins of all the subtypes. The biological activity of both molecules was examined using DFT calculation. This study may provide some insight into developing of new therapies in HIV-1 treatment by interrupting protein-protein interaction.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00318-4.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392817","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}

{"title":"Network pharmacology and in silico approach to study the mechanism of quercetin against breast cancer.","authors":"Tejveer Singh, Mahi Rastogi, Kulbhushan Thakur","doi":"10.1007/s40203-025-00306-8","DOIUrl":"10.1007/s40203-025-00306-8","url":null,"abstract":"<p><p>Breast cancer is a significant health concern among females with an estimated 2.3 million cases reported worldwide in 2022. Traditional treatment methods have now developed resistance and various adverse effects, highlighting an urgent need for attention. Therefore, it is advisable to substitute these conventional therapies with innovative medications. Quercetin is a flavonoid, commonly found in various vegetables and fruits and have been shown to possess anti-cancer properties. Network pharmacology is a comprehensive approach that has significantly assisted in investigating the potential of quercetin as a therapeutic option for breast cancer. The first step includes target fishing for quercetin-targeted genes in breast cancer through various online available databases. All intersecting genes were analysed for the phenotypic- genotypic correlation via online VarElect analysis tool. Using the result from the result the GO enrichment and pathway enrichment analysis was done on 52 common genes; followed by PPI network construction and based on topological parameters top 8 genes were filtered. Based on theVenny2.1 and then GEPIA and HPA analysis the key target were identifies as ABCC1, ABCC4, AKT1, ABCB1, CYP1B1, CYP19A1, ABCB4 and ABCG2. Further, Molecular docking was done to investigate the possible interaction of the identified gene with quercetin. Our finding shows quercetin is the potential natural drug that can treat breast cancer effectively. Quercetin interacts with ABCC1, ABCC4, AKT1, ABCB1, CYP1B1, CYP19A1, ABCB4, and ABCG2 at cellular as well as molecular level. The ADMET analysis suggests the bioavaibility of quercetin is around 0.55. Suggesting that quercetin satisfies drug-likeness rules but may face challenges like low bioavailability, which can be enhanced through structural modifications or formulations (e.g., nanoparticles). The molecular docking result assures the interaction of quercetin with the ABCC1, ABCC4, AKT1, ABCB1, CYP1B1, CYP19A1, ABCB4, and ABCG2 with the binding affinity of - 7.2, - 10.1, - 10.4, - 8.0, - 8.2, - 8.2, - 9.0 and - 8.9 respectively. These results suggest quercetin has a stable interaction with the ABCC4 gene. Considering this interaction the quercetin molecules can rescue the cellular condition by inducing apoptosis, inhibiting proliferation, and suppressing metastasis. Quercetin, a natural compound found in fruits and vegetables, has been found to have significant therapeutic roles in treating breast cancer. It inhibits cell cycle arrest, promotes apoptosis, and reduces blood vessel formation. It also reverses drug resistance and has antioxidant and anti-inflammatory properties. This study concludes that the therapeutic influence of quercetin plays a significant role in treating breast cancer and aids in the advancement of the clinical application of quercetin in future studies.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384615","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}

{"title":"Multi-scale computational modeling to identify novel chemical scaffolds as trehalose-6-phosphate phosphatase inhibitors to combat <i>Burkholderia pseudomallei</i>.","authors":"Sara Noor, Mohammad Abdullah Aljasir, Maryam Bashir, Kalsoom Khan, Sajjad Ahmad, Syed Ainul Abideen, Saifullah Khan, Farhan Siddique, Hamza Ahmad, Khudija Ghani, Madiha Iqbal, Muhammad Irfan, Abbas Khan, Dong-Qing Wei","doi":"10.1007/s40203-025-00309-5","DOIUrl":"10.1007/s40203-025-00309-5","url":null,"abstract":"<p><p><i>Burkholderia pseudomallei</i> causes melioidosis, a deadly infection having high fatality rates (20-50%) and antibiotic resistance, however, there's no effective drug or vaccine available. Trehalose is a vital sugar for <i>B. pseudomallei</i> which influences the pathogen resilience and pathogenicity. This proposed computational strategy focuses on developing novel drugs against Trehalose-6-phosphate Phosphatase (TPP) to combat infections. This study found three novel drugs from Asinex, Zinc, Chembridge, and Drugbank databases through a comprehensive structure-based virtual screening. The process screened the top three compounds: BDG_34042863, BDF_33738612, and DB00139 along with control (2-methyl-6-phenoxytetrahydro-2 H-pyran-3,4,5-triol) with a binding energy score of -8.8 kcal/mol, -8.4 kcal/mol, and - 7.7 kcal/mol, -6.4 kcal/mol respectively. In a molecular dynamics simulation, the Ligand-protein complexes demonstrated substantial non-covalent interactions as well as a stable docked intermolecular binding conformation. Throughout the MDS (molecular dynamic simulation) period, the studied compounds showed stable consistent interactions; there were no noticeable changes in the interactions or binding mode. The BDG_34042863, BDF_33738612, and DB00139 had a mean deviation of 4.04, 7.18, and 7.10 measured in Å, respectively. In addition, the simulation trajectories of complexes underwent MM/GBSA analysis, which revealed binding affinity scores of -33.39, -41.1, -49.16, and - 41.29 measured in kcal/mol for the control, BDG_34042863, BDF_33738612, and DB00139, respectively. According to DFT Analysis, BDF_33738612 showed the smallest energy gap (0.46 eV), indicating high reactivity, while DB00139 showed the largest energy gap (5.66 eV), illustrating good kinetic stability compared to the control. The compounds exhibit notable differences in reactivity and stability levels as their HOMO-1 to LUMO + 1 and HOMO-2 to LUMO + 2 orbitals have greater energy gaps, ranging from 5.06 eV to 6.69 eV and 5.66 eV to 7.09 eV, respectively. The compounds also had favorable pharmacokinetic characteristics and were categorized as druglike. Among the selected compounds, BDF_33738612 demonstrated the most promising findings followed by BDG_34042863 and DB00139. The compounds may be employed in an experimental study to examine their anti-TPP activity against <i>B. pseudomallei</i>.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00309-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124295","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}

{"title":"Allosteric activation of AMPK ADaM's site by structural analogs of Epigallocatechin and Galegine: computational molecular modeling investigation.","authors":"Mohnad Abdalla, Abdeen Tunde Ogunlana, Modinat Wuraola Akinboade, Ridwan Olajire Muraina, Oyindamola Anthonia Adeosun, Onyekachi Juliet Okpasuo, Olamide Tosin Olaoba, Abdulaziz Alouffi, Aqel Albutti, Zeyad Kurdee, Nouf Omar AlAfaleq, Ajibola Hannah Fatoberu, Temitope Isaac Adelus","doi":"10.1007/s40203-025-00311-x","DOIUrl":"10.1007/s40203-025-00311-x","url":null,"abstract":"<p><p>5'-Adenosine Monophosphate Protein Kinase (AMPK) is a central protein involved in cellular energy homeostasis, turning on catabolic pathways when the energy level is depleted and inhibiting anabolic pathways utilizing ATP. AMPK is implicated in several diseases including but not limited to diabetes, cancer, and cardiovascular diseases. Regulation of AMPK is cogent for restoring cellular energy levels which mediates the pathways leading to these diseases. Allosteric activation of AMPK via a novel ADaM site is intended for study in this case. In the search for AMPK activators, this study engaged a database for a virtual screening campaign through the ZINC15 database involving pharmacophoric modeling of two reported natural bioactive AMPK activators- Galegine and Epigallocatechin. Generated pharmacophores were targeted against the AMPK-ADaM site by employing various tools within the structure-based drug discovery process among which include consensus molecular docking, physicochemical profiling, ADMET, and molecular dynamics simulation. Advanced methods such as molecular mechanics (MM/GBSA) and quantitative structure-activity relationship (QSAR) were also performed. This investigation revealed promising pharmacophores that show better interactions and pharmacokinetic properties compared to the standards. This study proposes further development of these pharmacophores into potential drugs with better efficacies that could enhance the activation of the AMPK-ADaM site in ameliorating the aforementioned diseases.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00311-x.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081875","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}

{"title":"From phytomedicine to conventional drug research, to look for new drug molecule against monkey pox virus; a molecular docking, virtual screening and ADME analysis.","authors":"Pritam Goswami, Emmanuel Gabriel Fakola, Sayak Ghosh, Shubhamoy Ghosh, Satadal Das","doi":"10.1007/s40203-025-00310-y","DOIUrl":"10.1007/s40203-025-00310-y","url":null,"abstract":"<p><p>Globally, traditional and complementary therapies (such as homeopathy, phytotherapy and herbal medications) are becoming increasingly prevalent alongside modern medical care. The therapeutic substances used in homeopathy and other traditional complementary medicine disciplines are derived from these traditional applications. Numerous notable clinical and preclinical studies have shown their impact during COVID-19. This study aims to investigate the potential antiviral effects of medicinal alkaloids against the monkeypox virus in the current scenario. The structures of 47 known phytochemicals of commonly used medicines in CAM were obtained from PubChem in SDF format, minimized, and then docked against the 3D crystal structure of monkeypox virus methyltransferase VP39 (PDB: 8B07). The results were analyzed, and compounds with significant docking scores were further evaluated. The docking results showed that six compounds-Sarsaponin, Luteolin, Quercetin, Apigenin, and Ducimarine-had better docking scores than Tecovirimat, a standard drug used in managing monkeypox. Additionally, most compounds exhibited better docking scores than Cidofovir, another drug used against monkeypox. Interaction analysis revealed that hydrogen bonding, pi-pi T-shaped, and pi-alkyl interactions were responsible for the observed docking scores. Key amino acid residues involved in the interaction between the compounds and monkeypox virus methyltransferase VP39 included GLY 96, LEU 159, PHE 115, VAL 139, VAL 116, GLY 68, ARG 140, ILE 94, ASN 156, and ARG 156. Five phytochemicals-Luteolin, Quercetin, Apigenin, Sarsaponin, and Ducimarine-show strong potential as monkeypox virus methyltransferase inhibitors. Apigenin and Ducimarine are particularly promising due to their favorable profiles, including no PAINS alerts and good drug-like properties. Sarsaponin, while highly permeable, has high lipophilicity, which may limit its use. Luteolin and Quercetin also show potential but require further investigation due to PAINS alerts.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082096","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}