Pub Date : 2025-03-31DOI: 10.1016/j.amolm.2025.100079
Shankar Gharge , Charushila V. Balikai , Sachin Gudasi
This study explores the therapeutic potential of fatty acids (FA1-FA12) in the treatment of diabetes mellitus, focusing on their modulation of lipid-sensing nuclear receptors PPARδ/γ. Network pharmacology analysis highlighted key pathways involved in diabetes, including PI3K-Akt, MAPK, and insulin signaling, with targets such as PPAR, INSR, SLC2A4, and AKT1, suggesting a multi-target approach to disease modulation. To investigate their mechanism of action, a pharmacophore model was developed based on the PPAR-γ inhibitor Pioglitazone, offering insights into the essential structural features for ligand binding. Molecular docking studies revealed that FA1 and FA2 exhibited favorable binding affinities at the active sites of both PPAR-γ and PPAR-δ and MD trajectory analysis to evaluate binding orientation and stability of the molecules and the energy profiles of the molecules FA1 (Palmitic acid) and FA2 (Myristic acid), both in complex with the both PPAR-γ and PPAR-δ protein, were assessed. Additionally, computational analyses, including DFT and ADMET predictions, provided valuable information on the electronic and physicochemical properties of the fatty acids. Although these compounds displayed promising lipophilicity and permeability, their poor aqueous solubility indicates the need for optimization in drug development. Overall, this study lays a foundation for the exploration of fatty acids as potential therapeutic agents for diabetes, particularly through their modulation of PPARδ/γ activity for glycemic regulation.
{"title":"Structure-based insights into fatty acid modulation of lipid-sensing nuclear receptors PPARδ/γ for glycemic regulation","authors":"Shankar Gharge , Charushila V. Balikai , Sachin Gudasi","doi":"10.1016/j.amolm.2025.100079","DOIUrl":"10.1016/j.amolm.2025.100079","url":null,"abstract":"<div><div>This study explores the therapeutic potential of fatty acids (FA1-FA12) in the treatment of diabetes mellitus, focusing on their modulation of lipid-sensing nuclear receptors PPARδ/γ. Network pharmacology analysis highlighted key pathways involved in diabetes, including PI3K-Akt, MAPK, and insulin signaling, with targets such as PPAR, INSR, SLC2A4, and AKT1, suggesting a multi-target approach to disease modulation. To investigate their mechanism of action, a pharmacophore model was developed based on the PPAR-γ inhibitor Pioglitazone, offering insights into the essential structural features for ligand binding. Molecular docking studies revealed that FA1 and FA2 exhibited favorable binding affinities at the active sites of both PPAR-γ and PPAR-δ and MD trajectory analysis to evaluate binding orientation and stability of the molecules and the energy profiles of the molecules FA1 (Palmitic acid) and FA2 (Myristic acid), both in complex with the both PPAR-γ and PPAR-δ protein, were assessed. Additionally, computational analyses, including DFT and ADMET predictions, provided valuable information on the electronic and physicochemical properties of the fatty acids. Although these compounds displayed promising lipophilicity and permeability, their poor aqueous solubility indicates the need for optimization in drug development. Overall, this study lays a foundation for the exploration of fatty acids as potential therapeutic agents for diabetes, particularly through their modulation of PPARδ/γ activity for glycemic regulation.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759125","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}
Pub Date : 2025-03-28DOI: 10.1016/j.amolm.2025.100080
Manisha Mandal , Shyamapada Mandal
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causative agent of the COVID-19 pandemic, is still a cause of global concern, and therefore, safe and effective treatment is desperately needed. Bacteriocins produced by probiotic microorganisms displayed therapeutic potentiality against infectious diseases, including COVID-19. NSP1 (non-structural protein-1) of SARS-CoV-2 acts as a host translation inhibitor and reduces host immune function, thereby increasing viral pathogenicity and virulence. This information encouraged us to evaluate the inhibitory role of plantaricin JK (Pln-JK) against SARS-CoV-2 NSP1 using in silico methods. Herein, we used PatchMAN and CABS-dock webtools to perform molecular docking between SARS-CoV-2 NSP1 and Pln-JK, which generated NSP1-Pln-JK models. We used a peptide antiviral, peptide 5 (PEP5) as a reference. The top models (based on the lowest binding score and cluster density) of both systems were subjected to predict the binding affinity (ΔG, kcal/mol) and dissociation constant (KD, M) using PRODIGY. Pln-JK had excellent interaction with NSP1 displaying binding affinity of 9.1 kcal/mol and KD value of 2.1 × 10−7. The binding affinity and KD values for NSP1-PEP5 were −7.2 kcal/mol and 4.8 × 10−6 M (for PatchMan complex) and −5.9 kcal/mol and 4.8 × 10−5 M (for CABS-dock complex), respectively. HawkDock-based MM-GBSA binding free energies of CABS-dock and PatchMAN-generated complexes were −59.74 and −77.49 kcal/mol (for NSP1-Pln-JK) and −37.83 and −44.25 kcal/mol (for NSP1-PEP5), respectively. Further, molecular dynamic simulations-based MM-PBSA binding free energy confirmed NSP1-Pln-JK complex (−31.89 ± 0.91 kcal/mol) to be thermodynamically more stable than NSP1-PEP5 complex (−24.94 ± 0.6 kcal/mol). Pln-JK was predicted as non-allergic and non-toxic and thus emerged as a safe and effective molecule to combat SARS-CoV-2 infection. However, preclinical and clinical studies are needed before it can be considered as a prescription drug for the treatment of COVID-19.
{"title":"Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods","authors":"Manisha Mandal , Shyamapada Mandal","doi":"10.1016/j.amolm.2025.100080","DOIUrl":"10.1016/j.amolm.2025.100080","url":null,"abstract":"<div><div>SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causative agent of the COVID-19 pandemic, is still a cause of global concern, and therefore, safe and effective treatment is desperately needed. Bacteriocins produced by probiotic microorganisms displayed therapeutic potentiality against infectious diseases, including COVID-19. NSP1 (non-structural protein-1) of SARS-CoV-2 acts as a host translation inhibitor and reduces host immune function, thereby increasing viral pathogenicity and virulence. This information encouraged us to evaluate the inhibitory role of plantaricin JK (Pln-JK) against SARS-CoV-2 NSP1 using <em>in silico</em> methods. Herein, we used PatchMAN and CABS-dock webtools to perform molecular docking between SARS-CoV-2 NSP1 and Pln-JK, which generated NSP1-Pln-JK models. We used a peptide antiviral, peptide 5 (PEP5) as a reference. The top models (based on the lowest binding score and cluster density) of both systems were subjected to predict the binding affinity (ΔG, kcal/mol) and dissociation constant (K<sub>D</sub>, M) using PRODIGY. Pln-JK had excellent interaction with NSP1 displaying binding affinity of 9.1 kcal/mol and K<sub>D</sub> value of 2.1 × 10<sup>−7</sup>. The binding affinity and K<sub>D</sub> values for NSP1-PEP5 were −7.2 kcal/mol and 4.8 × 10<sup>−6</sup> M (for PatchMan complex) and −5.9 kcal/mol and 4.8 × 10<sup>−5</sup> M (for CABS-dock complex), respectively. HawkDock-based MM-GBSA binding free energies of CABS-dock and PatchMAN-generated complexes were −59.74 and −77.49 kcal/mol (for NSP1-Pln-JK) and −37.83 and −44.25 kcal/mol (for NSP1-PEP5), respectively. Further, molecular dynamic simulations-based MM-PBSA binding free energy confirmed NSP1-Pln-JK complex (−31.89 ± 0.91 kcal/mol) to be thermodynamically more stable than NSP1-PEP5 complex (−24.94 ± 0.6 kcal/mol). Pln-JK was predicted as non-allergic and non-toxic and thus emerged as a safe and effective molecule to combat SARS-CoV-2 infection. However, preclinical and clinical studies are needed before it can be considered as a prescription drug for the treatment of COVID-19.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738267","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}
Pub Date : 2025-03-26DOI: 10.1016/j.amolm.2025.100078
Eric Gyamerah Ofori , Foster Kyei , Emmanuel Ayitey Tagoe , Ansumana Sandy Bockarie , Samuel Mawuli Adadey , Osbourne Quaye , Michael Buenor Adinortey , Gordon Akanzuwine Awandare , Cynthia Ayefoumi Adinortey
Background
Antibiotic resistance jeopardizes the effectiveness of conventional treatment regimens for Helicobacter pylori infections, and this remains a major global health concern. H. pylori genes mutations negatively affect actions of most first line antibiotics. This study aimed to perform mutational analysis on H. pylori antibiotic resistance genes in Ghanaian patients diagnosed with dyspepsia.
Materials and methods
Antrum gastric biopsies were taken from 169 study participants, minced in Brain Heart Infusion broth and cultured. Sensitivity to antibiotics of H. pylori isolates was determined by disc diffusion. Extracted DNA were amplified and antibiotic resistance genes gyrA, pbp1, and rdxA sequenced. Resistance genes were analysed for base and point mutations using online databases and Ugene 45.0 software.
Results
Using rapid urease test, H. pylori infection prevalence was estimated to be 61%. Phenotypically, no sensitivity was recorded for metronidazole, amoxicillin, clarithromycin, and amoxicillin-clavulanic acid against the tested isolates. Resistance to levofloxacin was found to be 40% while 20% was recorded for each of tetracycline and ciprofloxacin. Mutations identified included G242 C/A, T254I, and S417T for pbp1 gene in amoxicillin resistance; K2N, Q6H, Q50Stop, E75K, R90K, G98S, H99P, R131K, and A183V for rdxA gene; N87I/T, A97V, M191I, V199 M/A, H200Y, and G208E for gyrA gene in levofloxacin resistance.
Conclusions
There is high H. pylori antibiotic resistance in the region with amoxicillin, metronidazole, amoxicillin-clavulanic acid and clarithromycin showing no sensitivity to tested isolates. Tetracycline and ciprofloxacin may be more appropriate therapeutic regimen options against H. pylori. Observed resistance could be due to mutations in rdxA, pbp1, and gyrA genes.
{"title":"Mutational analysis of antibiotic resistance genes in Helicobacter pylori from Ghanaian dyspepsia patients: Implications for treatment strategies","authors":"Eric Gyamerah Ofori , Foster Kyei , Emmanuel Ayitey Tagoe , Ansumana Sandy Bockarie , Samuel Mawuli Adadey , Osbourne Quaye , Michael Buenor Adinortey , Gordon Akanzuwine Awandare , Cynthia Ayefoumi Adinortey","doi":"10.1016/j.amolm.2025.100078","DOIUrl":"10.1016/j.amolm.2025.100078","url":null,"abstract":"<div><h3>Background</h3><div>Antibiotic resistance jeopardizes the effectiveness of conventional treatment regimens for <em>Helicobacter pylori</em> infections, and this remains a major global health concern. <em>H. pylori</em> genes mutations negatively affect actions of most first line antibiotics. This study aimed to perform mutational analysis on <em>H. pylori</em> antibiotic resistance genes in Ghanaian patients diagnosed with dyspepsia.</div></div><div><h3>Materials and methods</h3><div>Antrum gastric biopsies were taken from 169 study participants, minced in Brain Heart Infusion broth and cultured. Sensitivity to antibiotics of <em>H. pylori</em> isolates was determined by disc diffusion. Extracted DNA were amplified and antibiotic resistance genes <em>gyrA</em>, <em>pbp1</em>, and <em>rdxA</em> sequenced. Resistance genes were analysed for base and point mutations using online databases and Ugene 45.0 software.</div></div><div><h3>Results</h3><div>Using rapid urease test, <em>H. pylori</em> infection prevalence was estimated to be 61%. Phenotypically, no sensitivity was recorded for metronidazole, amoxicillin, clarithromycin, and amoxicillin-clavulanic acid against the tested isolates. Resistance to levofloxacin was found to be 40% while 20% was recorded for each of tetracycline and ciprofloxacin. Mutations identified included G242 C/A, T254I, and S417T for <em>pbp1</em> gene in amoxicillin resistance; K2N, Q6H, Q50Stop, E75K, R90K, G98S, H99P, R131K, and A183V for <em>rdxA</em> gene; N87I/T, A97V, M191I, V199 M/A, H200Y, and G208E for <em>gyrA</em> gene in levofloxacin resistance.</div></div><div><h3>Conclusions</h3><div>There is high <em>H. pylori</em> antibiotic resistance in the region with amoxicillin, metronidazole, amoxicillin-clavulanic acid and clarithromycin showing no sensitivity to tested isolates. Tetracycline and ciprofloxacin may be more appropriate therapeutic regimen options against <em>H. pylori</em>. Observed resistance could be due to mutations in <em>rdxA</em>, <em>pbp1,</em> and <em>gyrA</em> genes.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724093","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}
Pub Date : 2025-03-24DOI: 10.1016/j.amolm.2025.100077
Sarkar M.A. Kawsar , Rahnuma Tabassum , Nasrin Sultana Munia , Suraj N. Mali , Chin-Hung Lai , Jannatul Ferdous , Ferdausi Ali
<div><div>Nucleoside derivatives have contributed to the clinical and pharmaceutical fields as medicinal agents and approved drugs. The reaction of lauroyl chloride with cytosine β-D-riboside, i.e., cytidine (<strong>1</strong>) in DMF/Et<sub>3</sub>N, was the initiator step leading to 5′-<em>O</em>-(lauroyl)cytidine (<strong>2</strong>). Compound (<strong>2</strong>) was reacted with various acylating agents and penetrated to give 2′,3′-di-<em>O</em>-acyl derivatives (<strong>3</strong>–<strong>6</strong>). Physicochemical, spectroscopical, and elemental analysis methods were used to confirm the structure of the synthesized derivatives. <em>In vitro</em> antimicrobial tests, coupled with PASS prediction, revealed that these derivatives are highly effective against distinct pathogenic bacteria. Compared with the standard nystatin, compound <strong>5</strong> exhibited excellent antifungal efficacy against <em>Aspergillus flavus</em> and <em>Aspergillus niger</em>. Molecular docking analysis was performed to evaluate the binding interactions with the FimH lectin domain from <em>E. coli</em> K12 and urate oxidase (Uox) from <em>Aspergillus flavus</em>. For the FimH lectin domain, the binding affinities range from −2.35 to −9.32 kcal/mol (PyRx) and from −0.764 to 115.318 kcal/mol (iGEMDOCK), where compound <strong>2</strong> exhibited the highest binding affinity and outperformed the standard azithromycin, forming hydrogen bonds with ASN A:138, GLN A:133, ASP A:54, ASN A:46, PHE A:1, and ASP A:47, along with Pi-alkyl interactions with TYR A:48. Similarly, compound <strong>5</strong>, among the other synthesized compounds, strongly bound to Uox, with docking scores of −8.65 kcal/mol (PyRx) and −119.145 kcal/mol (iGEMDOCK), interacting with key residues such as THR A:173, LEU A:170, PHE A:258, and HIS A:256 through van der Waals forces, Pi‒Pi hydrophobic interactions, and hydrogen bonding. The RMSD, RMSF, and Rg analyses revealed that the docked complexes 4XO8:<strong>2</strong> and 1R4U:<strong>5</strong> exhibited stable protein‒ligand interactions, with no significant structural deviations observed during the 100 ns MD simulations. The hydrogen bonding and SASA results further support the stability of these complexes. According to DFT and FMO studies, compound <strong>5</strong> should exhibit the highest chemical reactivity because it has the smallest Egap (4.84 eV). In silico, ADMET and toxicity studies were used to evaluate the pharmacokinetic characteristics, drug-likeness, and toxicity parameters of the newly synthesized compounds. Finally, SAR study was performed to predict any subsequent changes in the antimicrobial activities of these compounds modified at various positions in their structure, especially those modified with [CH<sub>3</sub>(CH<sub>2</sub>)<sub>10</sub>CO] and {CH<sub>3</sub>(CH<sub>2</sub>)<sub>14</sub>CO}] groups. These results suggest that derivatives of lauroyl cytidine have great promise as antimicrobial agents for treat
{"title":"Potential antimicrobial properties of cytosine β-D-riboside derivatives through molecular dynamics and molecular docking exploration with bacterial and fungal proteins","authors":"Sarkar M.A. Kawsar , Rahnuma Tabassum , Nasrin Sultana Munia , Suraj N. Mali , Chin-Hung Lai , Jannatul Ferdous , Ferdausi Ali","doi":"10.1016/j.amolm.2025.100077","DOIUrl":"10.1016/j.amolm.2025.100077","url":null,"abstract":"<div><div>Nucleoside derivatives have contributed to the clinical and pharmaceutical fields as medicinal agents and approved drugs. The reaction of lauroyl chloride with cytosine β-D-riboside, i.e., cytidine (<strong>1</strong>) in DMF/Et<sub>3</sub>N, was the initiator step leading to 5′-<em>O</em>-(lauroyl)cytidine (<strong>2</strong>). Compound (<strong>2</strong>) was reacted with various acylating agents and penetrated to give 2′,3′-di-<em>O</em>-acyl derivatives (<strong>3</strong>–<strong>6</strong>). Physicochemical, spectroscopical, and elemental analysis methods were used to confirm the structure of the synthesized derivatives. <em>In vitro</em> antimicrobial tests, coupled with PASS prediction, revealed that these derivatives are highly effective against distinct pathogenic bacteria. Compared with the standard nystatin, compound <strong>5</strong> exhibited excellent antifungal efficacy against <em>Aspergillus flavus</em> and <em>Aspergillus niger</em>. Molecular docking analysis was performed to evaluate the binding interactions with the FimH lectin domain from <em>E. coli</em> K12 and urate oxidase (Uox) from <em>Aspergillus flavus</em>. For the FimH lectin domain, the binding affinities range from −2.35 to −9.32 kcal/mol (PyRx) and from −0.764 to 115.318 kcal/mol (iGEMDOCK), where compound <strong>2</strong> exhibited the highest binding affinity and outperformed the standard azithromycin, forming hydrogen bonds with ASN A:138, GLN A:133, ASP A:54, ASN A:46, PHE A:1, and ASP A:47, along with Pi-alkyl interactions with TYR A:48. Similarly, compound <strong>5</strong>, among the other synthesized compounds, strongly bound to Uox, with docking scores of −8.65 kcal/mol (PyRx) and −119.145 kcal/mol (iGEMDOCK), interacting with key residues such as THR A:173, LEU A:170, PHE A:258, and HIS A:256 through van der Waals forces, Pi‒Pi hydrophobic interactions, and hydrogen bonding. The RMSD, RMSF, and Rg analyses revealed that the docked complexes 4XO8:<strong>2</strong> and 1R4U:<strong>5</strong> exhibited stable protein‒ligand interactions, with no significant structural deviations observed during the 100 ns MD simulations. The hydrogen bonding and SASA results further support the stability of these complexes. According to DFT and FMO studies, compound <strong>5</strong> should exhibit the highest chemical reactivity because it has the smallest Egap (4.84 eV). In silico, ADMET and toxicity studies were used to evaluate the pharmacokinetic characteristics, drug-likeness, and toxicity parameters of the newly synthesized compounds. Finally, SAR study was performed to predict any subsequent changes in the antimicrobial activities of these compounds modified at various positions in their structure, especially those modified with [CH<sub>3</sub>(CH<sub>2</sub>)<sub>10</sub>CO] and {CH<sub>3</sub>(CH<sub>2</sub>)<sub>14</sub>CO}] groups. These results suggest that derivatives of lauroyl cytidine have great promise as antimicrobial agents for treat","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704154","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}
Pub Date : 2025-03-21DOI: 10.1016/j.amolm.2025.100076
Gourav Choudhir , Israil , Faiza Iram , Mohammad Shahid , Anas Shamsi , Md. Imtaiyaz Hassan , Asimul Islam
Staphylococcus aureus is a primary hospital-acquired infection-causing bacteria that is becoming resistant to many antibiotics. Its infection sites range from skin to soft tissue. The development of drugs for managing Staphylococcus aureus infection is urgently required. Targeting the enzymes involved in bacteria maintaining the integrity of cell walls could provide advances compared to other targets. Integrating molecular modeling approaches with drug-likeness properties identified the metabolites with affinity and safety to use. Molecular docking results showed that three metabolites with promising binding affinities to FmtA and interactions with the vital amino acid residues are essential in catalytic activity. The drug likeliness analysis showed that selected metabolites do not have any violations of Lipinski rules. A molecular dynamics simulation study revealed that metabolites, bisorbibutenolide and Koninginin A, exhibited the most stable complexes with FmtA. Bisorbibutenolide and Koninginin A also formed hydrogen bonds with FmtA throughout the simulation. These findings suggest that bisorbibutenolide and Koninginin A have the potential for further development as an anti-Staphylococcus aureus agent via targeting FmtA. Moreover, comprehensive experimental studies are necessary to validate these computational findings.
{"title":"Antibacterial potential of Trichoderma bioactive metabolites in managing Staphylococcus aureus infection: Integrated molecular modeling approaches","authors":"Gourav Choudhir , Israil , Faiza Iram , Mohammad Shahid , Anas Shamsi , Md. Imtaiyaz Hassan , Asimul Islam","doi":"10.1016/j.amolm.2025.100076","DOIUrl":"10.1016/j.amolm.2025.100076","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> is a primary hospital-acquired infection-causing bacteria that is becoming resistant to many antibiotics. Its infection sites <em>r</em>ange from skin to soft tissue. The development of drugs for managing <em>Staphylococcus aureus</em> infection is urgently required. Targeting the enzymes involved in bacteria maintaining the integrity of cell walls could provide advances compared to other targets. Integrating molecular modeling approaches with drug-likeness properties identified the metabolites with affinity and safety to use. Molecular docking results showed that three metabolites with promising binding affinities to FmtA and interactions with the vital amino acid residues are essential in catalytic activity. The drug likeliness analysis showed that selected metabolites do not have any violations of Lipinski rules. A molecular dynamics simulation study revealed that metabolites, bisorbibutenolide and Koninginin A, exhibited the most stable complexes with FmtA. Bisorbibutenolide and Koninginin A also formed hydrogen bonds with FmtA throughout the simulation. These findings suggest that bisorbibutenolide and Koninginin A have the potential for further development as an anti-<em>Staphylococcus aureus</em> agent via targeting FmtA. Moreover, comprehensive experimental studies are necessary to validate these computational findings.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686911","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}
Medicinal plants have long played a pivotal role in traditional medicine, and their integration into modern healthcare is gaining recognition for their potential in treating a range of conditions, including obesity and infectious diseases. Their bioactive compounds offer a natural, sustainable alternative to synthetic drugs, with significant therapeutic benefits. This review focuses on the recent advances of medicinal plants in addressing two major global health challenges: obesity and infectious diseases. In modern medicine, these plants are valued for their ability to manage weight by influencing metabolic processes such as fat oxidation, insulin sensitivity, and inflammation. Additionally, their antimicrobial properties offer effective solutions against drug-resistant pathogens, presenting a complementary approach to conventional treatments. Through a comprehensive analysis of bioactive compounds, the review investigates their mechanisms, including enzyme inhibition, modulation of immune response, and disruption of microbial growth and biofilm formation. Key findings indicate that these phytochemicals demonstrate both anti-obesity and antimicrobial activities, with potential to reduce inflammation, improve metabolic health, and combat drug-resistant infections. In essence, medicinal plants hold significant promise as natural therapeutic agents for managing obesity and infectious diseases. Their ability to target multiple biological pathways simultaneously makes them effective in addressing the complex interplay between metabolic disorders and immune dysfunction.
{"title":"Current insights on the effects of medicinal plants in the management of obesity and infectious diseases: An update from 2020","authors":"Ezichi Favour Ofoezie , Chinwendu Angela Ogbonna , Ezinne Tiffany George , Chioma Juliet Anunobi , Sandra C. Olisakwe , Simeon Babarinde , Chidera Godson Chukwuemeka , Uzochukwu Eric Ogbonna , Chibuzo Collette Amafili , Justina Onyinyechi Omaba , Henry Nnaemeka Ogbonna","doi":"10.1016/j.amolm.2025.100075","DOIUrl":"10.1016/j.amolm.2025.100075","url":null,"abstract":"<div><div>Medicinal plants have long played a pivotal role in traditional medicine, and their integration into modern healthcare is gaining recognition for their potential in treating a range of conditions, including obesity and infectious diseases. Their bioactive compounds offer a natural, sustainable alternative to synthetic drugs, with significant therapeutic benefits. This review focuses on the recent advances of medicinal plants in addressing two major global health challenges: obesity and infectious diseases. In modern medicine, these plants are valued for their ability to manage weight by influencing metabolic processes such as fat oxidation, insulin sensitivity, and inflammation. Additionally, their antimicrobial properties offer effective solutions against drug-resistant pathogens, presenting a complementary approach to conventional treatments. Through a comprehensive analysis of bioactive compounds, the review investigates their mechanisms, including enzyme inhibition, modulation of immune response, and disruption of microbial growth and biofilm formation. Key findings indicate that these phytochemicals demonstrate both anti-obesity and antimicrobial activities, with potential to reduce inflammation, improve metabolic health, and combat drug-resistant infections. In essence, medicinal plants hold significant promise as natural therapeutic agents for managing obesity and infectious diseases. Their ability to target multiple biological pathways simultaneously makes them effective in addressing the complex interplay between metabolic disorders and immune dysfunction.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738266","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}
Pub Date : 2025-03-19DOI: 10.1016/j.amolm.2025.100074
Md. Nur Kabidul Azam , Md Nasir Ahmed , Partha Biswas , Amia Kandker , Md. Mohaimenul Islam Tareq , Labib Shahriar Siam , Md. Nazmul Hasan
Varicella-Zoster Virus (VZV), causing chickenpox and potentially severe later-life complications, is traditionally treated by the Musahar tribe in Bangladesh using Molineria capitulata in a polyherbal formulation. This plant is also recognized in other regions for its anti-infective properties. This study aimed to evaluate the ethnomedicinal efficacy of Molineria capitulata against VZV using computational drug development approaches and to review its traditional medicinal uses. An ethnomedicinal survey was conducted, followed by QSAR, molecular docking, molecular dynamics simulation, ADMET and MM-GBSA analysis to assess potential treatments for VZV. Literature searches on PubMed and Google Scholar provided additional insights into the traditional antimicrobial uses of the plant. Twenty-four phytochemicals were screened against VZV thymidine kinase, revealing three with significant binding affinity (less than −10 kcal/mol): capituloside, curcapital, and pilosidine. These compounds showed strong protein interactions and stability in 100 ns simulations. Pilosidine had the highest docking score (−12.471 kcal/mol), followed by capituloside (−12.213 kcal/mol) and curcapital (−11.360 kcal/mol). Valacyclovir, the control, had a lower score (−5.807 kcal/mol). Pharmacokinetic profiles and QSAR analysis indicated their potential as lead compounds. Capituloside and pilosidine were effective against Herpes, Influenza, and Hepatitis B, while curcapital was effective against CMV, Herpes, Influenza, and Adenovirus. The physicochemical properties of these compounds highlight their significant potential as antiviral agents. The MM-GBSA evaluation indicated that among the complexes, the pilosidine-protein complex had the greatest free binding energy, with a value of −67.15 kcal/mol. Molineria capitulata holds promise for antiviral therapy development, and validating the therapeutic potential of capituloside, curcapital, and pilosidine against varicella-zoster virus requires comprehensive in-vitro and in-vivo studies.
{"title":"Unveiling potential antiviral phytochemicals from Molineria capitulata (Lour.) Herb. against varicella-zoster virus: Ethnomedicinal insights and computational analysis","authors":"Md. Nur Kabidul Azam , Md Nasir Ahmed , Partha Biswas , Amia Kandker , Md. Mohaimenul Islam Tareq , Labib Shahriar Siam , Md. Nazmul Hasan","doi":"10.1016/j.amolm.2025.100074","DOIUrl":"10.1016/j.amolm.2025.100074","url":null,"abstract":"<div><div>Varicella-Zoster Virus (VZV), causing chickenpox and potentially severe later-life complications, is traditionally treated by the Musahar tribe in Bangladesh using <em>Molineria capitulata</em> in a polyherbal formulation. This plant is also recognized in other regions for its anti-infective properties. This study aimed to evaluate the ethnomedicinal efficacy of <em>Molineria capitulata</em> against VZV using computational drug development approaches and to review its traditional medicinal uses. An ethnomedicinal survey was conducted, followed by QSAR, molecular docking, molecular dynamics simulation, ADMET and MM-GBSA analysis to assess potential treatments for VZV. Literature searches on PubMed and Google Scholar provided additional insights into the traditional antimicrobial uses of the plant. Twenty-four phytochemicals were screened against VZV thymidine kinase, revealing three with significant binding affinity (less than −10 kcal/mol): capituloside, curcapital, and pilosidine. These compounds showed strong protein interactions and stability in 100 ns simulations. Pilosidine had the highest docking score (−12.471 kcal/mol), followed by capituloside (−12.213 kcal/mol) and curcapital (−11.360 kcal/mol). Valacyclovir, the control, had a lower score (−5.807 kcal/mol). Pharmacokinetic profiles and QSAR analysis indicated their potential as lead compounds. Capituloside and pilosidine were effective against Herpes, Influenza, and Hepatitis B, while curcapital was effective against CMV, Herpes, Influenza, and Adenovirus. The physicochemical properties of these compounds highlight their significant potential as antiviral agents. The MM-GBSA evaluation indicated that among the complexes, the pilosidine-protein complex had the greatest free binding energy, with a value of −67.15 kcal/mol. <em>Molineria capitulata</em> holds promise for antiviral therapy development, and validating the therapeutic potential of capituloside, curcapital, and pilosidine against varicella-zoster virus requires comprehensive in-vitro and in-vivo studies.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686912","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}
Pub Date : 2025-03-14DOI: 10.1016/j.amolm.2025.100073
Namini M, Bhagya G, Manjari Sharma
Globally, lung cancer—more specifically, non-small cell lung cancer (NSCLC)—contributes significantly to the death toll from cancer. Recent advances in molecular research have identified key genetic mutations that drive tumor growth, including those in the EGFR, KRAS, ALK, and MET genes, accounting for around 80 % of lung cancers that are categorized as non-small cell lung cancer (NSCLC). The advent of targeted therapies such as Tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have revolutionized cancer treatment by specifically inhibiting oncogenic pathway. However, despite this advancements, treatment outcomes remain suboptimal due to intrinsic heterogeneity of cancers and the development of resistance mechanisms. The cancer treatment landscape is constantly changing to address these challenges and improve patient outcomes. Customization of cancer therapies through pharmacogenomics is hindered by tumor adapatability and resistance, limited prognostic biomarkers and suboptimal monotherapies, necessitating innovative research in adoptive therapies biomarker development and combination therapies. Ongoing trails aims to enhance treatment endurance via the advancement of combination regimens incorporating multiple targeted therapies or synergistic combination immunotherapy with chemotherapy. Ongoing research is focused on optimizing CRISPR-Cas9 delivery system, improving specificity and minimizing half target effect. Emphasizes the crucial role of molecular mutations, the advantages and disadvantages of targeted medicines, and the prospects for enhancing the effectiveness of lung cancer treatment results are all highlighted in this Review.
{"title":"Personalized approaches to lung cancer treatment: A review of targeted therapies, pharmacogenomics, and combination strategies","authors":"Namini M, Bhagya G, Manjari Sharma","doi":"10.1016/j.amolm.2025.100073","DOIUrl":"10.1016/j.amolm.2025.100073","url":null,"abstract":"<div><div>Globally, lung cancer—more specifically, non-small cell lung cancer (NSCLC)—contributes significantly to the death toll from cancer. Recent advances in molecular research have identified key genetic mutations that drive tumor growth, including those in the EGFR, KRAS, ALK, and MET genes, accounting for around 80 % of lung cancers that are categorized as non-small cell lung cancer (NSCLC). The advent of targeted therapies such as Tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have revolutionized cancer treatment by specifically inhibiting oncogenic pathway. However, despite this advancements, treatment outcomes remain suboptimal due to intrinsic heterogeneity of cancers and the development of resistance mechanisms. The cancer treatment landscape is constantly changing to address these challenges and improve patient outcomes. Customization of cancer therapies through pharmacogenomics is hindered by tumor adapatability and resistance, limited prognostic biomarkers and suboptimal monotherapies, necessitating innovative research in adoptive therapies biomarker development and combination therapies. Ongoing trails aims to enhance treatment endurance via the advancement of combination regimens incorporating multiple targeted therapies or synergistic combination immunotherapy with chemotherapy. Ongoing research is focused on optimizing CRISPR-Cas9 delivery system, improving specificity and minimizing half target effect. Emphasizes the crucial role of molecular mutations, the advantages and disadvantages of targeted medicines, and the prospects for enhancing the effectiveness of lung cancer treatment results are all highlighted in this Review.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100073"},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686910","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}
Ultra-processed foods (UPFs) are increasingly recognized as contributors to the pathogenesis of cardiovascular diseases (CVDs) and cancer due to their adverse compositional and mechanistic effects. UPFs, distinguished by their high content of unhealthy fats, sodium, refined sugars, and synthetic additives, significantly increase dyslipidemia, hypertension, and obesity, which are key risk factors for CVDs. Chronic consumption leads to systemic inflammation, gut microbiota dysbiosis, endothelial dysfunction, and oxidative stress. Additives such as artificial sweeteners and sodium nitrites in UPFs are associated with carcinogenesis through mechanisms involving genotoxicity and promotion of inflammatory microenvironments. This review critically evaluates existing epidemiological, mechanistic, and clinical evidence linking UPFs consumption to CVDs and cancer, synthesizing insights into their underlying pathophysiological mechanisms and highlighting disparities in disease burden across diverse populations. Epidemiological evidence demonstrates that UPFs constitute over 50% of daily caloric intake in Western diets, with each 10% increase in UPF consumption associated with a 12% rise in CVDs risk and a comparable increase in cancer incidence. Addressing the global surge in UPF consumption through dietary guidelines, regulatory policies, and public health initiatives may mitigate these risks, improve metabolic and cardiovascular health, and reduce cancer prevalence.
{"title":"The impact of ultra-processed foods on cardiovascular diseases and cancer: Epidemiological and mechanistic insights","authors":"Olorunfemi Oyewole Babalola , Ebenezer Akinnusi , Paul Olamide Ottu , Kpomah Bridget , Godspower Oyubu , Samuel Ayomikun Ajiboye , Sakariyau Adio Waheed , Amafili Chibuzo Collette , Hameedah Oluwatoyin Adebimpe , Chibuzo Valentine Nwokafor , Ebenezer Ayomide Oni , Precious Olayinka Aturamu , Opeyemi Iwaloye","doi":"10.1016/j.amolm.2025.100072","DOIUrl":"10.1016/j.amolm.2025.100072","url":null,"abstract":"<div><div>Ultra-processed foods (UPFs) are increasingly recognized as contributors to the pathogenesis of cardiovascular diseases (CVDs) and cancer due to their adverse compositional and mechanistic effects. UPFs, distinguished by their high content of unhealthy fats, sodium, refined sugars, and synthetic additives, significantly increase dyslipidemia, hypertension, and obesity, which are key risk factors for CVDs. Chronic consumption leads to systemic inflammation, gut microbiota dysbiosis, endothelial dysfunction, and oxidative stress. Additives such as artificial sweeteners and sodium nitrites in UPFs are associated with carcinogenesis through mechanisms involving genotoxicity and promotion of inflammatory microenvironments. This review critically evaluates existing epidemiological, mechanistic, and clinical evidence linking UPFs consumption to CVDs and cancer, synthesizing insights into their underlying pathophysiological mechanisms and highlighting disparities in disease burden across diverse populations. Epidemiological evidence demonstrates that UPFs constitute over 50% of daily caloric intake in Western diets, with each 10% increase in UPF consumption associated with a 12% rise in CVDs risk and a comparable increase in cancer incidence. Addressing the global surge in UPF consumption through dietary guidelines, regulatory policies, and public health initiatives may mitigate these risks, improve metabolic and cardiovascular health, and reduce cancer prevalence.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600515","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}
Sarcopenia, an age-related loss of skeletal muscle mass and function, impairs mobility, fragility, and quality of life. Despite progress in pathophysiology, molecular processes remain unknown. Recent research has investigated miRNAs as biomarkers for sarcopenia diagnosis and therapy. This work analyses differentially expressed genes (DEGs) and predicts miRNA-mRNA interactions using ML methods like XG-Boost and SHAP to find biomarkers.
Objective
This work evaluated the function of miRNA-mRNA interactions in sarcopenia pathogenesis and identified possible biomarkers by transcriptome analysis utilizing machine learning.
Methods
High-throughput mRNA sequencing datasets (GSE111006, GSE111010, and GSE111016) from GEO database were combined, pre-processed, and normalized using TPM and DESeq2 methods. XG-Boost regression analysis used 80/20 training and testing sets. SHAP analysis was used to evaluate model data and find significant DEGs. PPI networks were created using the STRING database, while miRNA-mRNA interactions were predicted using Encori and displayed with Cytoscape. The degree scores of miRNA-mRNA interactions were utilized to find biomarkers.
Results
XG-Boost and SHAP analysis revealed 20 influential DEGs linked to sarcopenia. With 97% accuracy, the model predicted accurately. PPI network research identified six hub genes: NTRK2, PCK1, DSP, SCD, MMRN1, and EDIL3. MiRNA-mRNA interaction analysis found miR-186–5p as the highest-degree biomarker candidate (36). MiR-186–5p was linked to muscle metabolism, hypertrophy, and exercise response.
Conclusion
The study found miR-186–5p to be a promising biomarker for sarcopenia using an integrated machine learning technique. The findings show that miR-186–5p may be a diagnostic and therapeutic target for sarcopenia, revealing its pathogenesis and enabling tailored treatments. Experimental research is needed to prove its therapeutic value.
{"title":"Computational framework for analyzing miRNA-mRNA interactions in sarcopenia: Insights into age-related muscular degeneration","authors":"Sarvesh Sabarathinam , Akash Jayaraman , Ramesh Venkatachalapathy , Subhiksha Shekar","doi":"10.1016/j.amolm.2025.100070","DOIUrl":"10.1016/j.amolm.2025.100070","url":null,"abstract":"<div><h3>Background</h3><div>Sarcopenia, an age-related loss of skeletal muscle mass and function, impairs mobility, fragility, and quality of life. Despite progress in pathophysiology, molecular processes remain unknown. Recent research has investigated miRNAs as biomarkers for sarcopenia diagnosis and therapy. This work analyses differentially expressed genes (DEGs) and predicts miRNA-mRNA interactions using ML methods like XG-Boost and SHAP to find biomarkers.</div></div><div><h3>Objective</h3><div>This work evaluated the function of miRNA-mRNA interactions in sarcopenia pathogenesis and identified possible biomarkers by transcriptome analysis utilizing machine learning.</div></div><div><h3>Methods</h3><div>High-throughput mRNA sequencing datasets (GSE111006, GSE111010, and GSE111016) from GEO database were combined, pre-processed, and normalized using TPM and DESeq2 methods. XG-Boost regression analysis used 80/20 training and testing sets. SHAP analysis was used to evaluate model data and find significant DEGs. PPI networks were created using the STRING database, while miRNA-mRNA interactions were predicted using Encori and displayed with Cytoscape. The degree scores of miRNA-mRNA interactions were utilized to find biomarkers<strong>.</strong></div></div><div><h3>Results</h3><div>XG-Boost and SHAP analysis revealed 20 influential DEGs linked to sarcopenia. With 97% accuracy, the model predicted accurately. PPI network research identified six hub genes: NTRK2, PCK1, DSP, SCD, MMRN1, and EDIL3. MiRNA-mRNA interaction analysis found miR-186–5p as the highest-degree biomarker candidate (36). MiR-186–5p was linked to muscle metabolism, hypertrophy, and exercise response.</div></div><div><h3>Conclusion</h3><div>The study found miR-186–5p to be a promising biomarker for sarcopenia using an integrated machine learning technique. The findings show that miR-186–5p may be a diagnostic and therapeutic target for sarcopenia, revealing its pathogenesis and enabling tailored treatments. Experimental research is needed to prove its therapeutic value.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594037","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}
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