Experimental parasitology最新文献

{"title":"Praziquantel effect on genetic diversity of wild rodent-derived Schistosoma mansoni in experimentally infected mice","authors":"Thayná Couto de Barros ,&nbsp;Roberto do Val Vilela ,&nbsp;Rosana Gentile ,&nbsp;Karina Varella ,&nbsp;Juberlan Silva Garcia ,&nbsp;Thiago dos Santos Cardoso ,&nbsp;Beatriz Elise de Andrade-Silva ,&nbsp;Aline dos Santos Moreira ,&nbsp;Beatriz de Lima Alessio Müller ,&nbsp;Alexandre Araujo Cunha dos Santos ,&nbsp;Daiani Cotrim de Paiva Campbell ,&nbsp;Arnaldo Maldonado Júnior","doi":"10.1016/j.exppara.2025.108963","DOIUrl":"10.1016/j.exppara.2025.108963","url":null,"abstract":"<div><div>Praziquantel (PZQ) is currently the only drug recommended by the World Health Organization (WHO) for treating schistosomiasis, raising concerns about potential resistance. Frequent use of PZQ may reduce the genetic diversity of <em>Schistosoma mansoni</em>, affecting its adaptability and survival. The objective of this study was to test the impact of Praziquantel treatment and population bottlenecks on the genetic diversity of <em>S. mansoni</em> by experimental infection using a wild strain isolated from naturally infected rodents. Experimental infections were conducted in outbred mice, which were infected with 120 cercariae, and treated with two different doses of PZQ (3 × 150 mg/kg and 3 × 300 mg/kg) at 50, 51, and 52 days post-exposure, and necropsied 15 days later. Microsatellites and MT-CO1 were used as molecular markers. An 85.5 % reduction in parasite load (p = 0.04) was observed after 300 mg/kg PZQ treatment, with greater efficacy in male worms. MT-CO1 analysis identified two haplotypes differing by one polymorphic site, with one haplotype representing 84.2 % of the population. Low genetic differentiation was observed for MT-CO1. All seven microsatellite loci studied exhibited polymorphisms, with 3–7 alleles per locus. Praziquantel treatment caused population bottleneck, reduced genetic variability in both dosage groups: IT150 (R_ST = 0.14043, p = 0.000) and IT300 (R_ST = 0.13610, p = 0.005), and eliminated alleles with low initial frequencies. We concluded that microsatellite markers showed genetic differentiation with elimination of rare alleles, confirming the genetic bottleneck effect due to treatment with PZQ.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"274 ","pages":"Article 108963"},"PeriodicalIF":1.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A network of RNA-binding and metabolic proteins evidenced in the Entamoeba histolytica nuclear proteome","authors":"Rodolfo Gamaliel Avila-Bonilla ,&nbsp;Jorge A. Velázquez Guzmán ,&nbsp;Esther Ramírez-Moreno ,&nbsp;Laurence A. Marchat","doi":"10.1016/j.exppara.2025.108965","DOIUrl":"10.1016/j.exppara.2025.108965","url":null,"abstract":"<div><div>Amoebiasis caused by the protozoan parasite <em>Entamoeba histolytica</em> is a serious leading cause of parasite-related death worldwide and there is a need for developing new safe and efficient control methods. The nuclear polyadenylation factor EhCFIm25 has been recently reported as a biochemical target in <em>E. histolytica,</em> being necessary for proliferation and parasite virulence. Interestingly, the prediction and experimental characterization of EhCFIm25 interactome revealed close relationships between nuclear proteins involved in gene expression regulation and typically cytoplasmic enzymes of redox and energy metabolism. Here, the description of the nuclear proteome of <em>E. histolytica</em> obtained by mass spectrometry analysis confirmed the presence of metabolic proteins in the nuclear compartment, which could have moonlight functions. Data are available via ProteomeXchange with identifier PXD056950. The predicted network of RNA-binding and metabolic proteins also evidenced the relevance of five metabolic enzymes in the coordination between energy and RNA metabolism, opening new perspectives for amoebiasis control.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"274 ","pages":"Article 108965"},"PeriodicalIF":1.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical formulation of Oseltamivir promotes clinical improvement and reduction of parasite load in BALB/c mice infected with Leishmania major","authors":"Victória Hannah Araújo de Almeida Passos ,&nbsp;Paulline Paiva Mendes de Souza Leal ,&nbsp;Pastora Pereira Lima Neta ,&nbsp;Evellyn Caroline Silva Melo ,&nbsp;Vinicius Santos Silva ,&nbsp;Glaucia Lais Nunes Lopes ,&nbsp;Matheus Oliveira do Nascimento ,&nbsp;Elvilene de Sousa Coelho ,&nbsp;Sérgio Paulo Lima Guerra ,&nbsp;Ana Karina Marques Fortes Lustosa ,&nbsp;Vitória de Cássia Coelho Rodrigues ,&nbsp;André Luis Menezes Carvalho ,&nbsp;Fernando Aécio de Amorim Carvalho ,&nbsp;Michel Mualem de Moraes Alves","doi":"10.1016/j.exppara.2025.108966","DOIUrl":"10.1016/j.exppara.2025.108966","url":null,"abstract":"<div><div>Leishmaniasis is a parasitic disease caused by protozoa of the genus <em>Leishmania</em>, the conventional treatments are expensives, high adverse reactions and long-term parenteral administration This study aimed to evaluate the therapeutic potential of the antiviral Oseltamivir (Osv) in microemulsion in the topical treatment of cutaneous leishmaniasis in BALB/c mice infected with <em>Leishmania major</em>. After infection, the mice were divided into five groups (Control, Amphotericin B 3 %, Osv 0.5 %, Osv 1 % and Osv 1 %+Amphotericin B 1.5 %) and treated for 21 days. Clinical parameters, such as body weight and lesion size, in addition to parasite load, hematological, biochemical and histopathological analyses were evaluated. A significant reduction in the parasite load was observed in the groups treated with Oseltamivir and Amphotericin B (70 %–76.5 %), when compared to the control group (95 %). Clinical evaluation showed fewer lesions in the treatment groups compared to the control group. Although Amphotericin B alone caused liver and kidney toxicity, treatment with Oseltamivir, alone or in combination with Amphotericin B, did not show any toxicity. In histopathological examination, the groups treated with Oseltamivir showed lower degrees of histopathological alterations. Thus, Oseltamivir, as monotherapy or in combination with Amphotericin B, proved to be effective and safe, representing a promising alternative in the treatment of cutaneous leishmaniasis.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"274 ","pages":"Article 108966"},"PeriodicalIF":1.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of essential oil from Maranta arundinacea L. against immature stages of dengue, filariasis, and malaria vectors and four mosquito predators","authors":"Pathalam Ganesan ,&nbsp;Jeyaraj Selvakumaran ,&nbsp;Natarajan Ganapathy Muthukumar ,&nbsp;Mariappan Muthukanagavel ,&nbsp;Subramanian Mutheeswaran ,&nbsp;Savarimuthu Ignacimuthu ,&nbsp;Rajakrishnan Rajagopal ,&nbsp;Ahmed Alfarhan ,&nbsp;Arokiyaraj Selvaraj","doi":"10.1016/j.exppara.2025.108964","DOIUrl":"10.1016/j.exppara.2025.108964","url":null,"abstract":"<div><div>Mosquitoes are significant vectors of infectious diseases, causing thousands of fatalities worldwide each year. This present study was to check the toxicity of essential oil (EO) from <em>Maranta arundinacea</em> L. against three mosquito species: <em>Anopheles stephensi, Culex quinquefasciatus</em> and <em>Aedes aegypti</em>. The immature stages were exposed to five different concentrations such as 3.125, 6.25, 12.5, 25 and 50 ppm; these were used to check the insecticidal activity according to WHO standard protocol with slight modification. The EO presented 100 % ovicidal toxicity against the eggs of treated three mosquitoes at 24 h. Strong mosquitocidal effects were observed, with LC₅₀ values of 5.0, 4.9 and 6.2 ppm for the larvae (3rd Instar) of <em>Anopheles, Culex</em> and <em>Aedes</em> species, respectively, at 24 h. However, no significant pupicidal toxicity was observed in any of the mosquito. Three main compounds were identified in the EO that might have contributed to its mosquitocidal properties. Toxicity assessments indicated that the EO from <em>M. arundinacea</em> did not adversely affect the tested natural predators such as <em>P. reticulata,</em> Dragon fly nymph, <em>D. indicus</em> and <em>G. affinis</em>. The EO was then formulated for field application, which confirmed its promising mosquitocidal activity (20–28 ppm), without any toxicity to tested natural predators. This study highlights the potential of EO from <em>M. arundinacea</em> in mosquito management, suggesting that it can serve as a possible substitute to synthetic chemicals, offering effective mosquito control with minimal environmental impact.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"274 ","pages":"Article 108964"},"PeriodicalIF":1.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystic echinococcosis susceptibility is increased by polymorphisms in the transporter associated with antigen processing 1 and 2 genes","authors":"Susan Jabbaripour ,&nbsp;Siamak Sandoghchian Shotorbani ,&nbsp;Adel Spotin ,&nbsp;Ehsan Ahmadpour ,&nbsp;Navid Shomali ,&nbsp;Mahmoud Mahami-Oskouei","doi":"10.1016/j.exppara.2025.108943","DOIUrl":"10.1016/j.exppara.2025.108943","url":null,"abstract":"<div><div>Susceptibility or resistance to various diseases, especially parasitic infections, largely depends on immune system function and genetics. Single nucleotide polymorphisms on the TAP1-637 and TAP2-379 genes may play a role in hydatidosis by affecting the immune system.</div><div>This study was conducted as a case-control study. After confirmation by serological ELISA method, blood samples were collected from 76 people with hydatid cyst and also from 76 healthy people. DNA was extracted from the samples and the ARMS-PCR technique was used to identify mutations. To evaluate the accuracy and ensure the PCR results, some samples were also sequenced in two groups with different genotypes.</div><div>Compared to the control group, the case group (infected group) had a higher frequency of the heterozygous Asp/Gly codon 637 of the TAP1 gene. In addition, the frequency of the Gly phenotype and allele was higher in the infected group (<em>P</em> &lt; 0.05). Furthermore, the infected group had a higher frequency of the heterozygous Val/Ile codon 379 of the TAP2 gene. The frequency of the Ile phenotype and allele was also higher in the infected group than in the control group (<em>P</em> &lt; 0. 05).</div><div>The results of this study showed that the Gly allele and Asp/Gly genotype in codon 637 of the TAP1 gene, as well as the Ile allele and Val/Ile genotype in codon 379 of the TAP2 gene are considered genetic risk factors for cystic echinococcosis.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"272 ","pages":"Article 108943"},"PeriodicalIF":1.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of therapeutics against PfPK6 protein of Plasmodium falciparum: Structure and Deep Learning approach","authors":"Sibasish Sarangi,&nbsp;Rajani Kanta Mahapatra","doi":"10.1016/j.exppara.2025.108947","DOIUrl":"10.1016/j.exppara.2025.108947","url":null,"abstract":"<div><div>The <em>Plasmodium falciparum</em> Protein Kinase 6 (PfPK6) is a serine/threonine protein kinase categorized under the CMGC group, displaying both cyclin-dependent kinases (CDKs) and mitogen-activated protein kinases (MAPKs) activity. Previous research has indicated that PfPK6 is expressed during the trophozoite and schizont stages of the <em>Plasmodium falciparum</em> asexual blood stage. Unlike typical cyclin-dependent kinases, PfPK6 demonstrates kinase activity independent of cyclin, making it a promising target for drug identification. In this study, we utilized a computational approach to identify a novel PfPK6 inhibitor through virtual screening of small inhibitor compounds from diverse datasets, employing a structure-based approach and a Deep Learning (DL) model. The most promising inhibitor molecule, TCMDC-132409 from the Tres Cantos Antimalarial Set, exhibited a binding affinity of −13.553 kcal/mol against PfPK6. Additionally, a 200ns molecular dynamics simulation study confirmed the stability of the binding mode, indicating the potential of TCMDC-132409 as an antiplasmodial inhibitor for further investigation.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"273 ","pages":"Article 108947"},"PeriodicalIF":1.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking, toxicity study and in vitro antimalarial evaluation of pyrazole substituted 1,3,5-triazine derivatives","authors":"Bonita Chetia ,&nbsp;Anshul Shakya ,&nbsp;Surajit Kumar Ghosh ,&nbsp;Sathishkumar Vinayagam ,&nbsp;Saurav Jyoti Patgiri ,&nbsp;Ipsita Pal Bhowmick ,&nbsp;Udaya Pratap Singh ,&nbsp;Hans Raj Bhat","doi":"10.1016/j.exppara.2025.108945","DOIUrl":"10.1016/j.exppara.2025.108945","url":null,"abstract":"<div><div>The development of resistance to antimalarial drugs such as chloroquine, amodiaquine, artemisinin, and antifolates is a major health concern, prompting more research into new antimalarial therapies. In the present study, we intend to develop pyrazole substituted 1,3,5-triazine derivatives <strong>7</strong>(<strong>a</strong>-<strong>j</strong>) as antimalarial agents. These compounds were synthesized using conventional methods and analyzed using various spectroscopic techniques. The docking results showed that compounds <strong>7j</strong> and <strong>7i</strong> exhibited an excellent binding interactions with PRO A:113, ILE A:164, SER A:111, PHE A:58, LEU A:46, LEU A:119, VAL A:45, ILE A:112 (−204.97to −118.41 kcal/mol) and TYR A:170, CYS A:15, PRO A:113, ILE A:112, ALA A:16, PHE A:58, MET A:55, SER A:111 (−216.24to −152.06 kcal/mol) against wild (1J3I) and quadruple mutant (1J3K) type of <em>Pf</em>-DHFR-TS. Compounds <strong>7j</strong> and <strong>7i</strong> exhibited considerable antimalarial efficacy against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains of <em>P. falciparum</em>, with IC₅₀ values ranging from 23.78 to 83.36 μM and 30.89–64.24 μM, respectively. These pyrazole-substituted 1,3,5-triazine derivatives could be utilized to find a novel class of <em>Pf</em>-DHFR-TS inhibitors.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"273 ","pages":"Article 108945"},"PeriodicalIF":1.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toll-like receptors and inflammatory cytokines in the skin of Acanthamoeba spp. infected immunocompetent and immunosuppressed mice","authors":"A. Wojtkowiak-Giera ,&nbsp;D. Kosik-Bogacka ,&nbsp;N. Łanocha-Arendarczyk ,&nbsp;A. Kolasa ,&nbsp;K. Kot ,&nbsp;P. Solarczyk ,&nbsp;M. Derda","doi":"10.1016/j.exppara.2025.108944","DOIUrl":"10.1016/j.exppara.2025.108944","url":null,"abstract":"<div><div><em>Acanthamoeba</em> spp. can cause opportunistic infections, such as cutaneous acanthamoebiasis (CA). Little is known about the role of TLRs and cytokines in the host skin during <em>Acanthamoeba</em> spp. infections. The study aimed to examine the gene and protein expression of TLR3, TLR7, IFN-γ, and IL-23 in the skin of mice experimentally infected with a clinical strain of <em>Acanthamoeba</em> spp. male BALB/c mice were assigned to four groups: group I (control group I) - with normal immunity (C, n = 5); group II (control group II) - with reduced immunity induced by methylprednisolone sodium succinate (MPS; CS, n = 5); group III - amoeba-infected hosts with normal immunity (A, n = 12); and group IV- amoeba-infected hosts with reduced immunity induced by MPS (AS, n = 12). The skin sections (2 cm × 2 cm) were collected from the animals at 8, 16, and 24 days post-infection (dpi). TLR3, TLR7, IFN-γ, and IL-23 gene and protein expressions were analyzed by quantitative real-time PCR and immunohistochemical staining.</div><div>In the immunocompetent hosts, we noted higher expressions of TLR3 and IL-23 at all-time points, except 8th dpi when IL-23 gene expression was downregulated compared to the control group. The mRNA expressions of TLR7 and IFN-γ were higher at 16 and 24 dpi in the skin of immunocompetent <em>Acanthamoeba</em> spp.-infected hosts than in the uninfected mice. In the course of acanthamoebiasis in the mice with reduced immunity, we found significant upregulation of TLR3, IL-23, and TLR7 gene expressions only at the beginning of infection compared to the control group. A similar relationship was observed for IFN-γ at 8 and 16 dpi.</div><div>The pathophysiology of <em>Acanthamoeba</em> infection in the skin is complex. The data presented in this paper add new insight, but they are not sufficient to explain the role of the studied receptors and cytokines. The clinical picture and mechanisms of host response appear to be influenced by the route of infection, immunological status and microorganisms carried within the parasites. CA remains a multifactorial phenomenon.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"273 ","pages":"Article 108944"},"PeriodicalIF":1.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application potential of arecoline hydrobromide for anti-Toxoplasma gondii","authors":"Xu Cheng ,&nbsp;Weifeng Yan ,&nbsp;Jingjie Xu ,&nbsp;Sihong Wang ,&nbsp;Chunmei Jin","doi":"10.1016/j.exppara.2025.108946","DOIUrl":"10.1016/j.exppara.2025.108946","url":null,"abstract":"<div><div>Although long-term chewing areca nut may cause cancer, it is very feasible to treat human or livestock diseases in a short period of time. In this study, arecoline hydrobromide (AH), which is extracted from <em>Areca catechu</em>, significantly inhibited the proliferation of tachyzoites of<em>Toxoplasma gondii</em> (<em>T. gondii</em>) <em>in vitro</em> and <em>in vivo</em>. Specially,<em>in vivo</em> AH effectively resisted liver damage originate from<em>T</em>. <em>gondii</em>. Furthemore, the survival and safety evaluation outcome indicated that AH can prolong survival period of mice infected with <em>T. gondii</em> at non-toxic and side-effect dose. Based on these advantages, AH is a candidate compound with great potential for the treatment of <em>T. gondii</em> infection and it may be used clinically in the future.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"273 ","pages":"Article 108946"},"PeriodicalIF":1.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico screening and molecular dynamic simulations of FDA-approved drugs as an inhibitor of trypanothione reductase of Leishmania donovani","authors":"Pooja Beniwal ,&nbsp;Chandra Kanta Bhusal ,&nbsp;Gajendra Choudhary ,&nbsp;Rakesh Sehgal ,&nbsp;Bikash Medhi ,&nbsp;Ajay Prakash ,&nbsp;Sukhbir Kaur","doi":"10.1016/j.exppara.2025.108942","DOIUrl":"10.1016/j.exppara.2025.108942","url":null,"abstract":"<div><div>Visceral leishmaniasis (VL) is mainly caused by <em>Leishmania donovani (Ld) and Leishmania (L.) infantum,</em> and it is prevalent in Brazil, India and East Africa. VL is a serious health issue, affecting millions of people worldwide and causing thousands of deaths annually. The current treatments for leishmaniasis are inadequate because of their low efficacy, toxicity and growing resistance, underscoring the pressing need to explore new drugs.</div><div>Among the various molecular targets explored, trypanothione reductase (TR) is of special relevance because of its crucial function in regulating the parasite's redox homeostasis. Inhibiting TR can disrupt the redox homeostasis of the parasites, offering a promising strategy for developing new drugs with improved efficacy and safety profiles. In this study, 3D structure model of TR was elucidated by homology modelling and potential novel inhibitors against <em>Leishmania donovani</em> TR (<em>Ld</em>TR) were identified by performing high-throughput virtual screening of 1615 FDA-approved drugs from the ZINC database <em>via</em> molecular docking, selecting top ligands on the basis of their high binding score and number of hydrogen bonds. These best hits are further subjected to Molecular Dynamics (MD) simulation and Molecular Mechanics Poisson- Boltzmann Surface Area (MM-PBSA) analysis. The results indicated that the binding scores of Dasatinib, Regorafenib, Bicalutamide, Raloxifene and Silodosin are −10.9 and −10.6, −10.1, −9.7 and −9.6 kcal/mol respectively. The lead compounds i.e. Dasatinib, Regorafenib, Bicalutamide, Raloxifene and Silodosin complexes with our target TR were found to be stable during MD simulation studies. Furthermore, MM-PBSA analysis demonstrated that these compounds had a high negative binding free energy. Thus, <em>in-silico</em> results showed that Dasatinib, Regorafenib, Bicalutamide and Raloxifene and Silodosin seem to have efficacy against TR for the treatment of VL. With further <em>in vitro</em> and <em>in vivo</em> investigations Dasatinib, Regorafenib, Bicalutamide, Raloxifene and Silodosin could be a good candidate of choice for combating leishmaniasis.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"272 ","pages":"Article 108942"},"PeriodicalIF":1.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}