Aspects of molecular medicine最新文献

{"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":"2025-06-01","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}

{"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 ,&nbsp;Chinwendu Angela Ogbonna ,&nbsp;Ezinne Tiffany George ,&nbsp;Chioma Juliet Anunobi ,&nbsp;Sandra C. Olisakwe ,&nbsp;Simeon Babarinde ,&nbsp;Chidera Godson Chukwuemeka ,&nbsp;Uzochukwu Eric Ogbonna ,&nbsp;Chibuzo Collette Amafili ,&nbsp;Justina Onyinyechi Omaba ,&nbsp;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":"2025-06-01","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}

{"title":"The impact of ultra-processed foods on cardiovascular diseases and cancer: Epidemiological and mechanistic insights","authors":"Olorunfemi Oyewole Babalola ,&nbsp;Ebenezer Akinnusi ,&nbsp;Paul Olamide Ottu ,&nbsp;Kpomah Bridget ,&nbsp;Godspower Oyubu ,&nbsp;Samuel Ayomikun Ajiboye ,&nbsp;Sakariyau Adio Waheed ,&nbsp;Amafili Chibuzo Collette ,&nbsp;Hameedah Oluwatoyin Adebimpe ,&nbsp;Chibuzo Valentine Nwokafor ,&nbsp;Ebenezer Ayomide Oni ,&nbsp;Precious Olayinka Aturamu ,&nbsp;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":"2025-06-01","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}

{"title":"Comprehensive review on anti-obesity effects of plant-derived compounds: Evidence from 3T3-L1 adipocytes and high-fat diet models","authors":"Sachin Gudasi,&nbsp;Mrityunjaya B. Patil","doi":"10.1016/j.amolm.2025.100089","DOIUrl":"10.1016/j.amolm.2025.100089","url":null,"abstract":"<div><div>Obesity, a multifactorial chronic disease, poses a growing global health concern, contributing to increased incidences of type 2 diabetes, cardiovascular diseases, osteoarthritis, and several cancers. Despite various pharmacological attempts targeting lipid metabolism enzymes, the associated adverse effects have led to numerous drug withdrawals, underscoring the urgent need for safer and more effective therapeutic strategies. In this context, the present study explores the <em>novel therapeutic potential</em> of plant-derived bioactives, specifically formulated using gold nanoparticles (GNPs), for the management of obesity. We systematically investigated the modulation of critical adipogenic and lipogenic regulatory proteins—C/EBP-α, PPAR-α, perilipin-1, adiponectin, FABP4, FAS, and ACC in 3T3-L1 pre-adipocytes and high-fat diet-induced obese mice. Our findings demonstrate that GNP-encapsulated phytoconstituents significantly reduce intracellular lipid accumulation by activating AMPK, a key energy sensor that downregulates pro-adipogenic and lipogenic genes (PPAR-α, C/EBP-α, AP2, SREBP-1c, ACC1, FAS, and LPL), while concurrently upregulating lipolytic and thermogenic genes (HSL, PGC-1α, and SIRT1) and enhancing adiponectin expression. The novelty of this study lies in the synergistic application of nanotechnology and traditional plant-based therapeutics to target obesity at a molecular level, offering a dual advantage of enhanced bioavailability and targeted action. These outcomes provide compelling evidence for the use of functionalized nanoparticles as a next-generation anti-obesity strategy, with potential translational value for clinical application.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles in thalassemia: Mechanisms, implications, and therapeutic potential","authors":"Shahzad Ali Jiskani","doi":"10.1016/j.amolm.2024.100061","DOIUrl":"10.1016/j.amolm.2024.100061","url":null,"abstract":"<div><div>Thalassemia is one of the most common inherited disorders of erythrocytes, caused by abnormalities in the production of globin chains. The clinical spectrum of thalassemia is broad, ranging from severe and persistent anemia that necessitates consistent blood transfusions to mild, asymptomatic conditions. Key contributors to thalassemia complications, particularly, in patients with β-thalassemia major, are ineffective erythropoiesis and iron overload. These complications can lead to a variety of severe health issues, including chronic inflammation, organ dysfunction, thrombosis, vascular abnormalities, and systemic iron overload. Extracellular vesicles (EVs) are tiny membrane-bound particles secreted from the plasma membranes of various cells during activation and cell death. Research has indicated that EVs are involved in numerous physiological and pathological processes, including inflammatory responses, clot formation, and vascular injury. Recently, the role of EVs has garnered interest of their potential as biomarkers, providing diagnostic and prognostic value of various disorders. In the context of thalassemia, elevated levels of EVs have been observed, highlighting their significance in the disease's cellular activities. The current review aims to examine the role of EVs in the pathogenesis of thalassemia, their implications, and their potential clinical applications. By exploring the involvement of EVs in the inflammatory and vascular complications associated with thalassemia, this review provides insights into their potential as therapeutic targets and diagnostic tools, offering a new perspective on managing this complex and multifaceted disorder.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146630","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 identification of phytochemicals as potential therapeutic agents to inhibit the HMG-CoA reductase activity using computational approach","authors":"Sheetal Dagar ,&nbsp;Anil Panwar ,&nbsp;Dushyant Gahalyan ,&nbsp;Neeru Redhu ,&nbsp;Mukesh Kumar ,&nbsp;Sunil Kumar ,&nbsp;Varruchi Sharma ,&nbsp;Heera Ram ,&nbsp;Ravikant Verma ,&nbsp;Anil Sharma","doi":"10.1016/j.amolm.2025.100086","DOIUrl":"10.1016/j.amolm.2025.100086","url":null,"abstract":"<div><div>Phytochemicals, have long been studied for various severe metabolic illnesses and degenerative diseases like heart disease and cancer because of their significant therapeutic effects. In animal cells, cholesterol serves a critical role being a component of cell membranes and essential for the normal functioning of precursor cells to some steroid hormones. Three-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) is converted into mevalonate by the HMG-CoA Reductase (HMGCR) enzyme to produce cholesterol. However, when cholesterol levels are high, it may result in atherosclerosis. Statins, also known as synthetic drugs which decrease cholesterol, are therefore designed to work by targeting this enzyme. For patients with dyslipidemia, the side effects of excessive statin therapy have proven alarming hence using natural plant-based inhibitors is a promising alternative. Computational approach helps to identified many drugs that can target HMG-CO A Reductase. In this study, using <em>in-silico</em> molecular docking via auto-dock, 20 medicinal plants with 120 phytochemicals, reported as having antihyperlipidemic activity through deep literature study, were screened as HMG-CoA reductase enzyme inhibitors. The virtual molecular docking results reveals that five bioactive compounds; Sominone, Guggulsterone, Phytosterol, Withanolide A and Basilol, had higher binding affinities towards the HMG-CO A Reductase having binding energies of −9.33, −8.99, −8.87, −8.58, and −8.48 kcal/mol, respectively. ADMET properties of selected compounds were analysed using swiss adme tool. Results showed that out of five compounds three follow Lipinski rule of five, having ADMET properties. The HMG-CoA reductase-ligand complex's stability was validated by RMSD, RMSF, Rg, H-bond results and principal component analysis. The resulting trajectories of converged period of MD were further exploited in MM-P/G/BSA calculations to derive accurate estimates of binding free energies. This leads one to the conclusion that five phytochemicals, Sominone, Guggulsterone, Phytosterol, Withanolide A and Basilol can serve as potential inhibitors in regulating HMGCR's function may assist the development of effective anti-hyperlipedemic drugs.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in silico Anti-diabetes mechanism of phytochemicals from Curculigo pilosa and its pharmacokinetic profiling via α-amylase inhibition","authors":"Damilola A. Omoboyowa ,&nbsp;Temitope C. Aribigbola ,&nbsp;Simbo T. Akinsulure ,&nbsp;Damilola S. Bodun ,&nbsp;Ezekiel A. Olugbogi ,&nbsp;Ebenezer A. Oni","doi":"10.1016/j.amolm.2025.100064","DOIUrl":"10.1016/j.amolm.2025.100064","url":null,"abstract":"<div><div>Diabetes mellitus is characterized by elevated blood glucose resulting from carbohydrate metabolism via glucose metabolizing enzymes such as α-amylase. <em>Curculigo pilosa</em> is traditionally used as herbal medication as anti-diabetes therapy but its mechanism of action is yet to be explored. This study investigates α-amylase inhibitory potential of <em>C. pilosa</em> using in vitro and in silico approaches. The ethylacetate, n-butanol and methanol extracts of <em>C. pilosa</em> were subjected to in vitro α-amylase inhibitory assay, followed by identification of the bioactive compounds from the most potent extract using HPLC. Integrated computational analyses were performed on ten (10) active compounds against α-amylase using Maestro Schrodinger (v2). The results of the in vitro α–amylase assay revealed n-butanol extract as the potent extract with IC₅₀ of 132.70 μg/mL, although the standard drug (acarbose IC₅₀ = 128.70 μg/mL) inhibits α-amylase better than the extracts. The HPLC result revealed the presence of ten (10) active compounds. Acarbose was observed to possess better binding affinity (−11.502 kcal/mol) than all the compounds but curculigoside was the hit compound with binding affinity of −8.797 kcal/mol. Some of the compounds showed appreciable inhibitory pIC₅₀ and fitness scores comparable to the standard drug. The pharmacokinetic profile revealed that none of the compounds violated more than one Lipinski's rule of five while the standard drug (acarbose) violated three (3) of the rules. The root mean square deviation shows reasonable level of stability within the simulation period for both curculigoside and acarbose. The result of in silico study showed significant inhibitory potential of the active compounds against α-amylase which was consistent with the in vitro inhibition of α amylase by the plant extract suggesting this as the possible mechanism of antidiabetes action of <em>C. pilosa</em>.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146624","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":"Unveiling potential antiviral phytochemicals from Molineria capitulata (Lour.) Herb. against varicella-zoster virus: Ethnomedicinal insights and computational analysis","authors":"Md. Nur Kabidul Azam ,&nbsp;Md Nasir Ahmed ,&nbsp;Partha Biswas ,&nbsp;Amia Kandker ,&nbsp;Md. Mohaimenul Islam Tareq ,&nbsp;Labib Shahriar Siam ,&nbsp;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":"2025-06-01","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}

{"title":"Antibacterial potential of Trichoderma bioactive metabolites in managing Staphylococcus aureus infection: Integrated molecular modeling approaches","authors":"Gourav Choudhir ,&nbsp;Israil ,&nbsp;Faiza Iram ,&nbsp;Mohammad Shahid ,&nbsp;Anas Shamsi ,&nbsp;Md. Imtaiyaz Hassan ,&nbsp;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":"2025-06-01","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}

{"title":"Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods","authors":"Manisha Mandal ,&nbsp;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_D, M) using PRODIGY. Pln-JK had excellent interaction with NSP1 displaying binding affinity of 9.1 kcal/mol and K_D value of 2.1 × 10⁻⁷. The binding affinity and K_D 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.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","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}